A dual-phase bioactive tissue repair scaffold and method of making

Abstract

The application discloses a kind of biphasic bioactive tissue repair scaffolds and preparation method, comprising the following steps: step 1: calcium phosphate ceramic powder is modified on surface, and the modified calcium phosphate ceramic powder is obtained;Step 2: the modified calcium phosphate ceramic powder, potassium sodium niobate piezoelectric ceramic powder, dispersing agent, photoinitiator, photosensitive resin are mixed evenly, and the light-cured resin slurry is obtained after ball milling;Step 3: according to the design, 3D printing model is constructed, and the light-cured resin slurry is printed according to 3D printing model, and the scaffold body can be obtained;Step 4: scaffold body is cleaned, and the required scaffold can be obtained after defatting sintering;The application can prepare biphasic bioactive tissue repair scaffold with good mechanical properties, efficient antitumor ability and better bone regeneration capacity, and provide technical support for the repair of bone tumor postoperative bone defect in clinic.

Description

Technical Field

[0001] This invention relates to the field of biomaterials for bone tissue repair, specifically to a biphasic bioactive tissue repair scaffold and its preparation method. Background Technology

[0002] Bone tumors are neoplastic diseases that occur in the bone or its surrounding tissues (such as bone marrow and cartilage). Currently, clinical treatment strategies for bone tumors mainly include surgical resection, chemotherapy, and radiotherapy. Surgical resection causes significant trauma and cannot completely remove tumor cells from the lesion, while chemotherapy and radiotherapy can cause serious adverse reactions.

[0003] For localized bone defects caused by bone tumor surgery, current clinical treatments include autologous bone grafting, allogeneic bone grafting, and the use of synthetic bone repair materials. While autologous bone grafting is the gold standard for bone defect repair, its bone supply is limited and cannot meet the requirements for large-area repair. Allogeneic bone, although solving the problem of limited bone source, is prone to absorption and deformation after implantation and has strong antigenicity, affecting treatment outcomes. Traditional calcium phosphate ceramic implants have poor mechanical properties and lack anti-tumor capabilities.

[0004] Successful tissue regeneration requires scaffolds with specific mechanical properties, suitable dimensions, and porosity. Current technologies for preparing tissue regeneration and repair scaffolds lack anti-tumor capabilities, and their ability to promote bone tissue regeneration is also limited.

[0005] 3D printing technology can precisely control the spatial distribution of printing paste, producing porous scaffolds with controllable dimensions and complex structures. The use of 3D printing technology to prepare biphasic bioactive tissue repair scaffolds with excellent mechanical properties, high anti-tumor activity, and good bone regeneration promotion capabilities is of great significance for the repair of bone defects after bone tumor surgery in clinical practice. Summary of the Invention

[0006] This invention addresses the problems existing in the prior art by providing a biphasic bioactive tissue repair scaffold and its preparation method.

[0007] The technical solution adopted in this invention is: a method for preparing a biphasic bioactive tissue repair scaffold, comprising the following steps:

[0008] Step 1: Surface modification of calcium phosphate ceramic powder to obtain modified calcium phosphate ceramic powder;

[0009] Step 2: Thoroughly mix the modified calcium phosphate ceramic powder, potassium sodium niobate piezoelectric ceramic powder, dispersant, photoinitiator, and photosensitive resin, and then ball mill to obtain a photocurable resin slurry;

[0010] The potassium sodium niobate piezoelectric ceramic is a potassium sodium niobate piezoelectric ceramic doped with manganese and cobalt.

[0011] The mass ratio of calcium phosphate ceramic powder to potassium sodium niobate piezoelectric ceramic powder is 16-19:1-4;

[0012] Step 3: Construct a 3D printing model according to the design, and print the photocurable resin slurry obtained in Step 2 according to the 3D printing model to obtain the bracket blank;

[0013] Step 4: The bracket blank obtained in Step 3 is cleaned, degreased and sintered to obtain the required bracket.

[0014] Furthermore, the calcium phosphate powder is composed of one or more of hydroxyapatite, β-tricalcium phosphate, and biphasic calcium phosphate in any proportion; the surface modifier of the calcium phosphate powder is composed of one or more of stearic acid, oleic acid, and fatty alcohol polyoxyethylene ether phosphate in any proportion; the amount of surface modifier added is 1 wt.% to 6 wt.% of the mass of the calcium phosphate ceramic powder.

[0015] Furthermore, the content of manganese and cobalt in the potassium sodium niobate piezoelectric ceramic is 0.2 mol%.

[0016] Furthermore, the photoinitiator is one or more of 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, 1-hydroxy-cyclohexyl-phenyl methyl ketone, phenylphosphine dioxide, methyl benzoylformate, isopropylthioxanthone, or 2-hydroxy-2-methyl-1-[4(2-hydroxyethoxy)phenyl]-1-propanone, mixed in any proportion.

[0017] Furthermore, the monomer of the photosensitive resin is one or more of 1,6-hexanediol diacrylate, dipropylene glycol diacrylate, tripropylene glycol diacrylate, and hydroxyethyl methacrylate mixed in any proportion; the mass of the photosensitive resin is 50 wt.% to 70 wt.% of the mass of the photocurable resin slurry.

[0018] Furthermore, in step 3, the 3D printing is performed using a digital light processing 3D printer;

[0019] The 3D printing exposure energy density is 6.20 Mj / cm³. 2 The exposure time is 2 seconds.

[0020] Furthermore, the degreasing and sintering process in step 4 is as follows:

[0021] First, raise the temperature to 300℃ and hold for 1 hour; then raise the temperature to 600℃ and hold for 5 hours; continue raising the temperature to 1100℃ and hold for 2 hours; finally, allow it to cool naturally to room temperature; the heating rate is 1-2℃ / min.

[0022] A biphasic bioactive tissue repair scaffold, wherein the scaffold has a biomimetic conch shell structure with a porosity of 65%.

[0023] Furthermore, the support is an initial layer composed of a cross-layered structure formed by horizontal and vertical rotation splicing of unit structures, and the initial layer is a multi-layered structure formed by rotational stacking and mirror stacking.

[0024] Furthermore, the unit structure includes two connected sub-units, each sub-unit including a first column 1, a second column 2, and a third column 3;

[0025] The second column 2 comprises four semi-elliptical columns with the same structure. The four second columns 2 are divided into two groups. The two semi-elliptical columns in each group are perpendicular to each other, and their planar portions are located in the same plane, forming two perpendicular planes. The two planes and the outer vertices of the four second columns 2 form a cube structure.

[0026] The subunit is located entirely inside the cubic structure;

[0027] The first column 1 is an elliptical column located at the center of the cube structure; the third column 3 consists of two elliptical columns that are perpendicular to each other within the cube space; the first column 1 and the third column 3 are perpendicular to each other within the cube space.

[0028] One end of the first column 1 is connected to a group of second columns 2, and the other end is connected to another group of second columns 2 and a third column 3;

[0029] The first column 1 is connected to the second column 2 and the third column 3 at a 45° bevel angle;

[0030] During the longitudinal and transverse splicing process of the unit structure, the first column 1 in different unit structures is located on the same straight line to form a single-layer structure, and the stacked single-layer structures form a layered initial layer.

[0031] The beneficial effects of this invention are:

[0032] (1) In this invention, calcium phosphate ceramic is combined with potassium sodium niobate to prepare a piezoelectric ceramic scaffold. Potassium sodium niobate can improve the mechanical properties of calcium phosphate ceramic, enhance its piezoelectric properties, and promote bone tissue regeneration. The doping of manganese and cobalt elements can improve the piezoelectric catalytic properties of the ceramic, increase its ROS generation rate under ultrasonic stimulation, and show a significant inhibitory effect on tumor cells.

[0033] (2) This invention uses 3D printing technology to prepare a porous scaffold with a biomimetic conch shell structure. The alternating soft-hard phase cross-layered structure and suitable porosity can prolong the residence time of blood and cells in the scaffold and promote bone tissue regeneration. The longitudinal three-level stacked structure can break the overall periodicity of the scaffold, effectively limit the transmission of force, realize layered deformation, inhibit the rapid expansion of shear bands, and improve the mechanical properties of the scaffold;

[0034] (3) The biphasic bioactive tissue repair scaffold prepared in this invention has good mechanical properties, high efficiency in anti-tumor activity and good bone regeneration ability, which has important clinical significance. Attached Figure Description

[0035] Figure 1 This is a schematic diagram of the initial layer structure in the support structure of the present invention; a is a schematic diagram of the sub-unit structure, b is a schematic diagram of the unit structure, and c is a schematic diagram of the initial layer structure.

[0036] Figure 2 The diagram shows the structure of the support of the present invention. a is a schematic diagram of the stacked structure, and b is a schematic diagram of the support structure.

[0037] Figure 3 The diagram shows the mechanical properties of the supports obtained in Embodiment 1 and Comparative Example 2 of the present invention. a is a schematic diagram of the deformation behavior under a given strain, and b is a schematic diagram of the stress-strain curve during the compression process.

[0038] Figure 4 The image shows the SEM image of the stent obtained in Embodiment 1 of the present invention. a is the result under low magnification, b is the result under high magnification, and c is the result of EDS energy dispersive spectroscopy analysis.

[0039] Figure 5 The image shows the SEM image of the stent obtained in Comparative Example 3 of this invention. a is the result under low magnification, b is the result under high magnification, and c is the result of EDS energy dispersive spectroscopy analysis.

[0040] Figure 6 The following are schematic diagrams of transmission electron microscopy (TEM) results of the piezoelectric ceramic powders used in the embodiments of the present invention: a is a schematic diagram of TEM results of potassium sodium niobate piezoelectric ceramic powders doped with manganese and cobalt used in Examples 1 and 2; b is a schematic diagram of TEM results of potassium sodium niobate piezoelectric ceramic powders used in Comparative Example 3.

[0041] Figure 7 The diagram shows the degradation results of the scaffold powder obtained in Examples 1 and 2 and Comparative Examples 1 and 3 of the present invention. a is the degradation efficiency curve, b is the statistical graph of the degradation rate k value, and c is the degradation kinetic curve.

[0042] Figure 8 This is a schematic diagram showing the anti-tumor and osteogenic effects of the scaffolds obtained in Embodiments 1 and 2 and Comparative Examples 1 and 3 of the present invention.

[0043] In the diagram, 1 represents the first column, 2 represents the second column, and 3 represents the third column. Detailed Implementation

[0044] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0045] A method for preparing a biphasic bioactive tissue repair scaffold includes the following steps:

[0046] Step 1: Surface modification of calcium phosphate ceramic powder to obtain modified calcium phosphate ceramic powder; the calcium phosphate powder is composed of one or more of hydroxyapatite, β-tricalcium phosphate, and biphasic calcium phosphate in any proportion. The surface modifier of calcium phosphate powder is composed of one or more of stearic acid, oleic acid, and fatty alcohol polyoxyethylene ether phosphate in any proportion; the amount of surface modifier added is 1 wt.% to 6 wt.% of the mass of calcium phosphate ceramic powder.

[0047] Step 2: Thoroughly mix the modified calcium phosphate ceramic powder, potassium sodium niobate piezoelectric ceramic powder, dispersant, photoinitiator, and photosensitive resin, and then ball mill to obtain a photocurable resin slurry;

[0048] The photoinitiator is one or more of 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, 1-hydroxy-cyclohexyl-phenyl ketone, phenylphosphine dioxide, methyl benzoylformate, isopropylthioxanthone, or 2-hydroxy-2-methyl-1-[4(2-hydroxyethoxy)phenyl]-1-propanone, mixed in any proportion.

[0049] The monomers of the photosensitive resin are one or more of 1,6-hexanediol diacrylate, dipropylene glycol diacrylate, tripropylene glycol diacrylate, and hydroxyethyl methacrylate, mixed in any proportion; the mass of the photosensitive resin is 50 wt.% to 70 wt.% of the mass of the photocurable resin slurry.

[0050] The potassium sodium niobate piezoelectric ceramic is a potassium sodium niobate piezoelectric ceramic doped with manganese and cobalt; the content of manganese and cobalt in the potassium sodium niobate piezoelectric ceramic is 0.2 mol.%. The mass ratio of calcium phosphate ceramic powder to potassium sodium niobate piezoelectric ceramic powder is 16-19:1-4.

[0051] Step 3: Construct a 3D printing model according to the design, and print the photocurable resin slurry obtained in Step 2 according to the 3D printing model to obtain the bracket blank; 3D printing is performed using a digital light processing 3D printer;

[0052] The 3D printing exposure energy density is 6.20 Mj / cm³. 2 The exposure time is 2 seconds.

[0053] The 3D printing model was constructed using Solidworks 3D modeling software.

[0054] Step 4: The bracket blank obtained in Step 3 is cleaned, degreased and sintered to obtain the required bracket.

[0055] The degreasing and sintering process is as follows:

[0056] First, raise the temperature to 300℃ and hold for 1 hour; then raise the temperature to 600℃ and hold for 5 hours; continue raising the temperature to 1100℃ and hold for 2 hours; finally, allow it to cool naturally to room temperature; the heating rate is 1-2℃ / min.

[0057] The support structure is a biomimetic conch shell structure with a porosity of 65%. The initial layer is a cross-layered structure formed by horizontal and vertical rotational splicing of unit structures. This initial layer then forms a multi-layered structure through rotational and mirror-stacking. For example... Figure 2 As shown, the following embodiments use a three-layer structure consisting of an initial layer, a rotation layer, and a mirror layer. The specific number of layers can be selected according to the actual situation.

[0058] unit structure such as Figure 1 As shown, it includes two connected sub-units, each sub-unit comprising a first pillar 1, a second pillar 2, and a third pillar 3;

[0059] The second column 2 comprises four semi-elliptical columns with the same structure. The four second columns 2 are divided into two groups. The two semi-elliptical columns in each group are perpendicular to each other, and their planar portions are located in the same plane, forming two perpendicular planes. The two planes and the outer vertices of the four second columns 2 form a cube structure.

[0060] The subunit is located entirely inside the cubic structure;

[0061] The first column 1 is an elliptical column located at the center of the cube structure; the third column 3 consists of two elliptical columns that are perpendicular to each other within the cube space; the first column 1 and the third column 3 have the same structure and are perpendicular to each other within the cube space.

[0062] One end of the first column 1 is connected to a group of second columns 2, and the other end is connected to another group of second columns 2 and a third column 3;

[0063] The first column 1 is connected to the second column 2 and the third column 3 at a 45° bevel angle;

[0064] During the longitudinal and transverse splicing process of the unit structure, the first column 1 in different unit structures is located on the same straight line to form a single-layer structure, and the stacked single-layer structures form a layered initial layer.

[0065] During the longitudinal and transverse splicing process of the unit structure, the first column 1 forms a supporting structure that penetrates a single-layer plane. After 180° longitudinal rotation and replication, the first column 1 forms a biomimetic seashell-like cross-layered initial structure with different orientations on different faces. The cross-layered structure formed by rotation and splicing has heterogeneous node connections. The nodes at both ends of the first column 1 have more spatial constraints and are considered as "soft phases," while other nodes with fewer constraints are considered as "hard phases."

[0066] The alternating soft-hard phase cross-layered structure can simulate the multi-material modulus differences in the structure of natural conch shells. 90° rotation and mirror stacking were used in the longitudinal stacking of the scaffolds. The diameters, lengths, and other parameters of the first, second, and third pillars were adjusted to ensure a porosity of 65%. Boolean operations were used to cut the scaffolds into φ6mm×10mm cylinders for subsequent fabrication of the scaffolds in various embodiments.

[0067] Longitudinal stacking is used to further improve the mechanical properties of the support. Mirror stacking and rotational stacking are used to break the overall periodicity, making it more difficult to transmit cross-layer forces, achieving layered deformation, and inhibiting the rapid expansion of shear bands.

[0068] Example 1

[0069] A method for preparing a biphasic bioactive tissue repair scaffold includes the following steps:

[0070] Step 1: Place the calcium phosphate powder in an anhydrous ethanol solution of fatty alcohol polyoxyethylene ether phosphate with a mass concentration of 6 wt.%. Stir until uniformly mixed; transfer to a ball mill jar, add ball milling beads with a ball-to-powder ratio of 1:1, and ball mill for 4 hours. After completion, dry, grind, and sieve to obtain a powder with good dispersibility and suspension stability.

[0071] Step 2: Weigh the modified calcium phosphate powder and manganese and cobalt-doped potassium sodium niobate powder at a mass ratio of 18:2. The content of manganese and cobalt in the potassium sodium niobate piezoelectric ceramic is 0.2 mol%.

[0072] Weigh out 55 wt.% of the photosensitive resin (obtained by polymerization of 1,6-hexanediol diacrylate) according to the total mass of the slurry, and add 3% of the total mass of the slurry dispersant and 2,4,6-trimethylbenzoyl-diphenylphosphine oxide. Transfer the mixture to a ball mill jar, add ball milling beads with a ball-to-material ratio of 1:1, and ball mill for 8 hours to obtain a photocurable resin slurry with uniform ceramic particle distribution.

[0073] Step 3: Using SolidWorks software, design a biomimetic conch shell unit structure. Obtain the support model through mirror stacking and rotational stacking, adjusting parameters to achieve a porosity of approximately 65%. The structure is as follows: Figure 1 and Figure 2 As shown.

[0074] Import the 3D printing model into the digital light processing 3D printer, adjust the scraper height and travel speed, and set the exposure energy density to 6.20 Mj / cm². 2 The exposure time is 2 seconds, and the scaffold blank is printed. The scaffold blank is removed with a spatula and placed in anhydrous ethanol for repeated ultrasonic cleaning three times, 10 minutes each time. After cleaning, it is placed in a muffle furnace for degreasing and sintering. The steps are as follows: heat up to 300℃ at a heating rate of 2℃ / min and hold for 1 hour; then heat up to 600℃ at a heating rate of 1℃ / min and hold for 5 hours; then heat up to 1100℃ at a heating rate of 2℃ / min and hold for 2 hours; finally, it is naturally cooled to room temperature to obtain the required scaffold.

[0075] Example 2

[0076] The other preparation steps in this embodiment are the same as in Example 1, except that the mass ratio of the modified calcium phosphate powder and the manganese and cobalt-doped potassium sodium niobate powder in step 2 is 19:1.

[0077] Comparative Example 1

[0078] A porous ceramic scaffold is described. The other preparation steps in this comparative example are the same as those in Example 1, except that only calcium phosphate ceramic powder is used in step 2.

[0079] Comparative Example 2

[0080] A porous ceramic scaffold is described. The other preparation steps of this comparative example are the same as those in Example 1, except that the 3D model in step 3 uses square holes as the unit structure.

[0081] Comparative Example 3

[0082] A porous ceramic scaffold is described. The other preparation steps in this comparative example are the same as those in Example 1, except that the potassium sodium niobate powder in step 2 is not doped with manganese and cobalt.

[0083] Mechanical property tests were conducted on Example 1 and Comparative Example 2, and the results are as follows: Figure 3 As shown. From Figure 3 As can be seen from Figure a, Comparative Example 2 exhibits overall structural collapse at 6% strain, with obvious brittle characteristics in the fractured portion; while Example 1, with its layered dispersed shear band design, achieves layered failure, with the damage confined to one layer at 6% strain, while the structural integrity of the remaining layers remains good. Its rotating stacked cross-layered structure effectively inhibits crack propagation across layers. Figure 3As can be seen from Figure b, in Comparative Example 2, the stress rises sharply in the initial stage of compression, reaches its peak at a strain of 1.5%, and then drops sharply to a low point, failing to provide effective mechanical support during subsequent compression. In contrast, the stress in Example 1 is more dispersed, with a slower stress rise in the initial stage of compression and a faster recovery to the original stress level during subsequent compression, providing more stable support. This demonstrates that the seashell-inspired bionic structure can effectively improve the mechanical properties of the support.

[0084] Electron microscopy analysis was performed on the scaffolds obtained in Example 1 and Comparative Example 3. The scanning electron microscopy results and EDS energy dispersive spectroscopy results of Example 1 and Comparative Example 3 are as follows: Figure 4 and Figure 5 As shown, the transmission electron microscopy results of the two piezoelectric powders used in Example 1 and Comparative Example 3 are as follows: Figure 6 As shown.

[0085] from Figure 4 and Figure 5 As can be seen, when potassium sodium niobate piezoelectric ceramic powder is incorporated, a sporadic flaky grain structure appears on the surface of the support, while when manganese and cobalt-doped potassium sodium niobate piezoelectric ceramic powder is incorporated, a high-density rod-shaped grain structure appears on the surface of the support.

[0086] from Figure 6 It can be seen that both pure potassium sodium niobate and manganese and cobalt-doped potassium sodium niobate are nanoscale. Pure potassium sodium niobate exhibits a typical irregular polyhedral structure, while manganese and cobalt-doped potassium sodium niobate exhibits a uniform cubic structure.

[0087] The scaffolds obtained in Examples 1 and 2, and Comparative Examples 1 and 3 were ground into powder for ultrasonic catalytic effect testing. The piezoelectric catalytic effect of the four scaffold powders under ultrasonication was evaluated by catalytic degradation of Rhodamine B dye solution (which has redox properties) by powders exhibiting piezoelectric effects. The dye solution concentration was 5 mg / L, prepared in 50 mL solutions. 0.2 g of ceramic powder was used for each solution, and the ultrasonic conditions were 180 W and 40 kHz. The four powders were mixed with Rhodamine B dye to the same concentration and stirred continuously in the dark for 30 min (generally, the powder reaches adsorption equilibrium after 30 min to avoid the powder's influence on dye color adsorption). Then, ultrasonication was continued for another 30 min under the same conditions. The absorbance of the solution at the excitation wavelength of 553 nm was measured after 30 min of stirring when the powder reached adsorption equilibrium, and every 5 min after the start of ultrasonication. A lower absorbance at the same excitation wavelength indicates a liquid color closer to transparency, meaning that the reddish Rhodamine B degradation effect is better, and the piezoelectric catalytic effect of the scaffold powder is more superior. The comparative results are shown below. Figure 7 As shown.

[0088] from Figure 7As can be seen from Figure a, under ultrasonic treatment, the Rhodamine B solution itself undergoes slight degradation; the degradation of Rhodamine B solution in Comparative Example 1 is almost the same as under ultrasonic conditions alone; however, under ultrasonic treatment, Examples 1, 2, and Comparative Example 3 exhibit a piezoelectric catalytic effect, causing the Rhodamine B solution to gradually degrade to almost transparent, indicating that the addition of potassium sodium niobate can improve the piezoelectric catalytic ability of the composite scaffold. Figure 7 As can be seen from Figures b and c, the degradation rate of Rhodamine B dye in Example 2 is much higher than that in Comparative Example 3, indicating that doping with manganese and cobalt can further improve the piezoelectric catalytic ability of potassium sodium niobate. Meanwhile, the degradation rate of Rhodamine B dye in Example 1 is higher than that in Example 2, indicating that the higher the content of manganese and cobalt-doped potassium sodium niobate piezoelectric ceramic, the better the piezoelectric catalytic ability of the scaffold powder.

[0089] The scaffolds obtained in the comparative and example cases were placed in bone tumor model animals. Antitumor section testing was performed at 4 weeks, and osteogenic section staining was performed at 20 weeks. The results are as follows: Figure 8 As shown in the figure, the composite ceramic scaffold exhibits superior antitumor and osteopromoting effects compared to the calcium phosphate ceramic scaffold. Furthermore, the manganese- and cobalt-doped potassium sodium niobate composite ceramic demonstrates significantly better antitumor and osteopromoting effects than the scaffold prepared from potassium sodium niobate ceramic powder. This indicates that manganese- and cobalt-doped potassium sodium niobate can degrade into manganese and cobalt ions in vivo, thereby achieving the goals of antitumor and osteopromoting effects.

[0090] This invention employs a biomimetic conch shell-inspired porous scaffold structure. By constructing a longitudinally stacked three-tiered structure, the overall periodicity of the scaffold is disrupted, making the transmission of cross-layer forces more difficult. This allows for layered deformation, inhibits the expansion rate of shear bands, and improves the mechanical properties of the scaffold. Under certain loads, the scaffold can effectively maintain structural integrity, providing sufficient mechanical support in the early stages of implantation. Furthermore, this asymmetric, cross-layered structure exhibits nodal heterogeneity. The alternating soft and hard phases, while mimicking the structure of a natural conch shell, effectively reduce fluid velocity, prolong blood residence time within the scaffold, promote efficient exchange of nutrients and metabolites, improve cell adhesion efficiency at the scaffold interface, and promote new bone ingrowth. Simultaneously, the porous structure of the scaffold allows for sufficient contact between cells and potassium sodium niobate, enabling the scaffold to inhibit tumor cells as much as possible under ultrasound, demonstrating highly effective anti-tumor capabilities. By doping potassium sodium niobate with manganese and cobalt to enhance the piezoelectric properties of calcium phosphate ceramics, piezoelectric biomaterials, which are semiconductor functional materials capable of converting mechanical energy into electrical energy, generate piezoelectric potential under ultrasonic mechanical action. This facilitates the generation, migration, and separation of charge carriers within the material, producing high-intensity reactive oxygen species (ROS) molecules, thus possessing the potential to become highly efficient sonosensitive agents. Sonodynamic therapy involves ultrasound-induced sonosensitive agents to generate high doses of cytotoxic ROS molecules, subsequently inducing oxidative stress in tumor cells, damaging biomolecules, and ultimately leading to tumor cell apoptosis or necrosis. Compared to traditional chemotherapy, physical therapy, and photothermal therapy, sonodynamic therapy offers advantages such as greater tissue penetration depth and higher safety. Furthermore, the doping of manganese and cobalt enhances the piezoelectric catalytic performance of potassium sodium niobate, improving the efficiency of ROS generation in the composite ceramic scaffold under ultrasonic action, thereby enhancing the antitumor ability of the composite scaffold.

[0091] In summary, this invention utilizes 3D printing technology to construct a biomimetic conch shell-structured porous scaffold with excellent mechanical properties. Its suitable porosity promotes the ingrowth of new bone tissue. Simultaneously, a composite ceramic scaffold integrating antitumor and osteogenic functions is constructed using manganese and cobalt-doped potassium sodium niobate composite calcium phosphate ceramic. This scaffold leverages enhanced sonodynamic antitumor activity, and the doping of manganese and cobalt ions further enhances its antitumor properties and endows it with angiogenic properties, thereby improving its osteogenic capacity. This provides an effective strategy for the repair of bone defects after bone tumor surgery in clinical practice. Compared with existing technologies, this invention represents a significant advancement.

Claims

1. A method for preparing a biphasic bioactive tissue repair scaffold, characterized in that, The method comprises the following steps: Step 1: surface modification of calcium phosphate ceramic powder to obtain modified calcium phosphate ceramic powder; Step 2: mixing the modified calcium phosphate ceramic powder, potassium sodium niobate piezoelectric ceramic powder, dispersant, photoinitiator and photosensitive resin uniformly, and then ball milling to obtain a photocuring resin slurry; The potassium sodium niobate piezoelectric ceramic is a manganese and cobalt doped potassium sodium niobate piezoelectric ceramic; The mass ratio of the calcium phosphate ceramic powder and the potassium sodium niobate piezoelectric ceramic powder is 16-19:1-4; Step 3: constructing a 3D printing model according to the design, and printing the photocuring resin slurry obtained in step 2 according to the 3D printing model to obtain a scaffold blank; Step 4: the scaffold blank obtained in step 3 is cleaned, degreased and sintered to obtain the required scaffold; The scaffold is an initial layer formed by transverse and longitudinal rotation splicing of a unit body structure into a cross-layer structure, and the initial layer is a multi-layer structure formed by rotation stacking and mirror stacking; the unit body structure comprises two sub-unit bodies connected, and the sub-unit body comprises a first column (1), a second column (2) and a third column (3); The second column (2) comprises four semihalf-elliptic columns with the same structure, and the four second columns (2) are divided into two groups; the two semihalf-elliptic columns in each group are perpendicular to each other, and the plane parts thereof are located in the same plane, and the two planes are perpendicular to each other; the two planes and the outer extension top points of the four second columns (2) form a cubic structure; The sub-unit body is located inside the cubic structure as a whole; The first column (1) is an elliptic column arranged at the center of the cubic structure, and the third column (3) is two elliptic columns arranged perpendicularly to each other in the cubic space; the first column (1) and the third column (3) are perpendicular to each other in the cubic space; One end of the first column (1) is connected with one group of second columns (2), and the other end is connected with another group of second columns (2) and the third column (3); The first column (1) is connected with the second column (2) and the third column (3) by 45° beveling; In the longitudinal and transverse splicing process of the unit body structure, the first columns (1) in different unit body structures are located on the same straight line to form a single-layer structure, and the single-layer structures are stacked to form a layered initial layer.

2. The method of claim 1, wherein the bi-phasic bioactive tissue repair scaffold is prepared by the steps of: The calcium phosphate ceramic powder is one or two or more of hydroxyapatite, β-tricalcium phosphate and biphasic calcium phosphate mixed in any ratio; the surface modifier of the calcium phosphate powder is one or two or more of stearic acid, oleic acid and fatty alcohol polyoxyethylene ether phosphate mixed in any ratio; and the addition amount of the surface modifier is 1 wt.%-6 wt.% of the mass of the calcium phosphate ceramic powder.

3. The method for preparing a biphasic bioactive tissue repair scaffold according to claim 1, characterized in that, The content of manganese and cobalt in the potassium sodium niobate piezoelectric ceramic is 0.2 mol.%.

4. The method for preparing a biphasic bioactive tissue repair scaffold according to claim 1, characterized in that, The photoinitiator is one or two or more of 2,4,6-trimethylbenzoyl-diphenyl phosphine oxide, 1-hydroxy-cyclohexyl-phenyl methanone, phenyl bisphosphine oxide, methyl benzoylformate, isopropyl thioxanthone or 2-hydroxy-2-methyl-1-[4(2-hydroxyethoxy)phenyl]-1-propanone mixed in any ratio.

5. The method for preparing a biphasic bioactive tissue repair scaffold according to claim 1, characterized in that, The monomer of the photosensitive resin is one or two or more of 1,6-hexanediol diacrylate, dipropylene glycol diacrylate, tripropylene glycol diacrylate, and hydroxyethyl methacrylate mixed in any ratio; the mass of the photosensitive resin is 50 wt.% to 70 wt.% of the mass of the photocuring resin slurry.

6. The method of claim 1, wherein the bi-phasic bioactive tissue repair scaffold is prepared by the steps of: In the step 3, 3D printing is performed by using a digital light processing 3D printer. 3D printing exposure energy density was 6.20 Mj / cm 2 , exposure time was 2 s.

7. The method for preparing a biphasic bioactive tissue repair scaffold according to claim 1, characterized in that, In the step 4, the debinding and sintering process is as follows: First, the temperature is raised to 300 DEG C and kept for 1 h; then the temperature is raised to 600 DEG C and kept for 5 h; then the temperature is continuously raised to 1100 DEG C and kept for 2 h; finally, the temperature is naturally cooled to room temperature; wherein the temperature raising rate is 1-2 DEG C / min.

8. The bi-phasic bioactive tissue repair scaffold prepared by the method according to any one of claims 1 to 7, characterized in that, The scaffold is a bionic conch shell structure, and the porosity thereof is 65%.

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