Traditional Chinese medicine active activated bone growth type support implant material and preparation method thereof

Abstract

The application discloses a traditional Chinese medicine active activated bone growth type support implant material and a preparation method thereof, and relates to the technical field of medical materials.The traditional Chinese medicine active activated bone growth type support implant material is composed of an organic-inorganic composite porous antibacterial support and a medicinal efficacy filler.Co hollow spheres loaded with carbon nanotubes, sodium alginate, nano-hydroxyapatite and transition metal carbide nanosheets are cross-linked and compounded to form the organic-inorganic composite porous antibacterial support, which not only has good mechanical properties and antibacterial properties, but also can stably bear more medicinal efficacy fillers and slowly release the medicinal efficacy fillers, and the medicinal efficacy fillers further improve the stability of the support structure.The synergistic effect of the two can significantly enhance the antibacterial property and osteogenesis of the implant material, and excellent bone repair effect is achieved.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically referring to a bone growth-activating support implant material made from traditional Chinese medicine and its preparation method. Background Technology

[0002] Bone defects caused by factors such as trauma, tumor resection, infection, and degenerative diseases have become one of the major problems that seriously affect patients' limb function and quality of life. Because bone tissue has a certain regenerative capacity, surgical intervention is generally not required for minor injuries or small bone defects. However, bone defects exceeding the critical size are difficult to heal naturally and must be accelerated through clinical intervention to promote bone defect repair and bone tissue regeneration.

[0003] Treatment methods for bone defects are mainly divided into autologous bone transplantation, allogeneic bone transplantation, and artificial bone materials. Autologous bone transplantation, which involves transplanting the patient's own bone tissue, effectively avoids post-operative immune rejection. However, its limited availability and serious donor site complications severely restrict its large-scale application. Allogeneic bone transplantation, while having a wide range of donor bone sources, carries the risk of bone repair failure. Artificial bone materials, on the other hand, possess excellent biocompatibility and bioactivity, promoting bone tissue repair and stimulating osteogenic and angiogenesis, demonstrating great application potential. Commonly used artificial bone repair materials mainly include bioceramic materials, polymeric materials, and metallic materials.

[0004] The existing technology currently suffers from the following main problems:

[0005] Bone defects are often accompanied by bacterial activity. However, artificial bone materials, as implants, have weak antibacterial properties, which further triggers inflammatory responses, limiting the repair and growth of bone tissue. In addition, the poor mechanical properties of a single artificial bone material are not conducive to the stability of the implant, which in turn limits the repair effect. Summary of the Invention

[0006] In view of the above situation and to overcome the defects of the prior art, the present invention proposes a bone growth-activating support implant material with Chinese medicine, comprising the following components in parts by weight: 10-20 parts of organic-inorganic composite porous antibacterial scaffold and 20-30 parts of drug-efficacy filler.

[0007] The organic-inorganic composite porous antibacterial scaffold comprises the following components in parts by weight: 10-15 parts sodium alginate, 10-20 parts transition metal carbide nanosheets, 5-8 parts nano hydroxyapatite, 20-30 parts Co hollow spheres loaded with carbon nanotubes, and 6-8 parts gluconolactone.

[0008] The medicinal filler comprises the following components in parts by weight: Epimedium 3-5 parts, Dioscorea opposita 3-5 parts, Drynaria fortunei 3-5 parts, Astragalus membranaceus 3-5 parts, Cervi cornu colla 3-5 parts, Boswellia carterii 3-5 parts, Cuscuta chinensis 3-5 parts, Commiphora myrrha 3-5 parts, Lycium barbarum 3-5 parts, Achyranthes bidentata 3-5 parts, Ligustrum lucidum 3-5 parts, Ostrea gigas 3-5 parts, and Rehmannia glutinosa 3-5 parts.

[0009] The preparation method of the organic-inorganic composite porous antibacterial scaffold specifically includes the following steps:

[0010] (1) Add 2.0-3.0g of lithium fluoride to 40mL of 30% hydrochloric acid solution, and slowly add 1.0-2.0g of titanium aluminum carbide while stirring at 50-60rpm. After the addition is complete, stir at 30-40℃ for 24-36h. Centrifuge the mixture at 2000-4000rpm for 5-10min to remove the supernatant. Wash the precipitate 3-5 times with 10% dilute hydrochloric acid, and then repeatedly centrifuge and wash with deionized water until the pH is 6.0. Add the washed precipitate to 100mL of deionized water. The colloidal solution was sonicated in an ice bath for 0.5-1 h, and then centrifuged at 4000-5000 rpm for 10-20 min. The upper colloidal solution was then filtered into a thin film using a vacuum circulating water filter and dried. The transition metal carbide has high strength and flexibility, which can withstand the mechanical stress during the bone repair process and provide necessary support. The transition metal carbide has antibacterial properties, which can reduce the risk of postoperative infection. The conductivity of the transition metal carbide can be used to apply electrical stimulation to promote osteoblast growth and bone tissue regeneration, thereby improving the success rate of bone repair. The result is a transition metal carbide nanosheet.

[0011] (2) Dissolve 19.8g sodium gluconate in 300mL of deionized water, add cobalt nitrate hexahydrate, stir evenly, turn on the preheating furnace, raise the temperature to 700-800℃ at a rate of 10℃ / min, then transfer the solution to the ultrasonic nebulizer, turn on the ultrasonic device and introduce nitrogen gas at 1.5L / min. The nitrogen gas can blow the product into the collection bottle filled with ethanol, collect the black solid, filter and wash with deionized water 3-5 times, vacuum dry, the hollow structure formed by the aggregation of Co nanoparticles reduces the weight of the implant material, reduces the pressure on the surrounding tissue, can also provide sufficient mechanical strength and have excellent elasticity, can withstand greater pressure, effectively reduce wear and damage, the porous characteristics of the hollow spheres are conducive to bone cell growth and angiogenesis, promote new bone formation, and obtain Co hollow spheres;

[0012] (3) Place the Co hollow spheres described in step (2) in a tube furnace, raise the temperature to 700°C at a rate of 8-10°C / min under an argon atmosphere of 80 mL / min, and then introduce a mixture of acetylene and hydrogen at a rate of 80 mL / min. Keep the temperature for 20-40 min, stop introducing acetylene and hydrogen, and lower the temperature to room temperature under argon protection. Using acetylene as a carbon source, dense carbon nanotubes grow in situ on the surface of the Co hollow spheres under the reducing action of hydrogen. This effectively prevents the accumulation and aggregation of hollow spheres, increases the contact area, and provides more active sites. It can adsorb active substances and achieve sustained release, improve the stability and effectiveness of active substances, and is conducive to better stimulating bone growth and bone repair, thus obtaining Co hollow spheres loaded with carbon nanotubes.

[0013] (4) Disperse the transition metal carbide nanosheets and nano hydroxyapatite described in step (1) in 50 mL of deionized water, sonicate for 1-2 h, centrifuge, freeze-dry the precipitate first, and then mix it evenly with the Co hollow spheres loaded with carbon nanotubes described in step (3). Then anneal it in a nitrogen environment at 350-400℃ for 1-2 h. The nano hydroxyapatite is first inserted into the interlayer spacing of the transition metal carbide nanosheets, which reduces the stacking of nanosheets and provides conditions for the subsequent filling of the Co hollow spheres loaded with carbon nanotubes. This further increases the specific surface area of ​​the material and the continuity and density of the network structure, which is conducive to loading more active substances and playing a more stable supporting role, thus obtaining the composite material.

[0014] (5) Disperse the composite material described in step (4) in 50 mL of deionized water, sonicate for 1-2 h, add 1.0-1.5 g of sodium alginate, stir magnetically for 20-30 min, and use it as a liquid to be used. Weigh 0.2-0.3 g of calcium carbonate and add it to 5 mL of deionized water, sonicate for 20-30 min, and then add the calcium carbonate suspension to the liquid to be used at a speed of 1000-2000 rpm. After dispersing evenly, add gluconolactone, stir evenly, transfer to a 24-well plate, and react at 4°C for 12-24 h. Then freeze-dry at -80°C for 36-48 h. Through the cross-linking of organic and inorganic materials, a complex and continuous dense porous structure is formed, which has excellent antibacterial and mechanical properties, can provide more stable support, and has abundant adsorption sites. It can load more drug components to achieve slow and stable release, reduce the occurrence of burst release effect, and play the dual role of drug and scaffold in promoting bone growth and bone repair, thus obtaining an organic-inorganic composite porous antibacterial scaffold.

[0015] Preferably, in step (2), the amount of cobalt nitrate hexahydrate added is 24.2-26.2g. The introduction of cobalt can reduce the adhesion rate of bacteria, endow it with certain antibacterial properties, reduce the risk of bacterial infection and inflammation, and promote macrophages to transform into the M2 phenotype, creating an immune environment conducive to bone regeneration. It can also promote the differentiation of osteoblasts, activate multiple signaling pathways related to bone resorption and bone formation, and accelerate the formation of new bone.

[0016] Preferably, in step (5), the amount of gluconolactone added is 0.6-0.8g. The weakly acidic environment formed by the hydrolysis of gluconolactone promotes the release of calcium ions from calcium carbonate to crosslink and form a gel. Gluconolactone can reduce the inflammatory response during bone repair, stimulate angiogenesis, improve local blood supply, provide more nutrients and oxygen for bone repair, stimulate osteoblast proliferation and differentiation, accelerate bone matrix synthesis, and thus promote new bone formation.

[0017] This invention also provides a method for preparing a bone growth-activating support implant material made from traditional Chinese medicine, specifically including the following steps:

[0018] S1. Place Epimedium, Dioscorea opposita, Drynaria fortunei, Astragalus membranaceus, deer antler glue, frankincense, Cuscuta chinensis, myrrh, Lycium barbarum, Achyranthes bidentata, Ligustrum lucidum, oyster shell, and Rehmannia glutinosa in a decoction machine with 10-15 times the amount of water and soak for 2-3 hours. Decoction 1-2 times, extracting by gentle boiling for 2-3 hours. Combine the decoctions, freeze-dry the residue for later use. Concentrate the collected filtrate to 1 / 6 to 1 / 5 of its original volume under vacuum pressure -0.06 MPa and temperature 40-50℃. Then pour the freeze-dried residue powder into the concentrated liquid and sonicate. After 30-40 minutes of magnetic stirring for 1-2 hours, the synergistic use of traditional Chinese medicine components can promote the expression of osteogenic-related factors (such as alkaline phosphatase, osteopontin, and osteocalcin) and activate multiple signaling pathways, thereby effectively activating the differentiation and proliferation of osteoblasts. It can also adsorb onto the surface of bacteria to prevent the absorption of nutrients or enter the bacteria to produce flocculation and thus produce antibacterial effects. Its antibacterial spectrum is relatively broad. At the same time, the form of lyophilized powder and concentrated liquid ensures the comprehensiveness and effectiveness of the drug efficacy, resulting in a drug efficacy filler.

[0019] S2. Immerse the organic-inorganic composite porous antibacterial scaffold in the medicated filler material described in step S1 for 2-3 hours. Remove and pre-treat the scaffold, then use a dropper to add the remaining medicated filler material drop by drop, allowing it to stand for 30-50 seconds after each addition. This immersion and drop-in method promotes the uniformity and stability of the medicated filler material. After addition, freeze-dry at -80℃ for 24-36 hours, then sterilize by UV irradiation for 8 hours in a clean bench. The medicated filler material loaded onto the organic-inorganic composite porous antibacterial scaffold improves the scaffold's mechanical properties and stability. The medicated filler material can induce osteoblasts to secrete… The extracellular matrix establishes a connection network, further enhancing the strength of the scaffold and its surrounding area. At the same time, the porous structure of the scaffold improves drug loading capacity and drug stability, enabling slow and continuous release of the drug-efficacy filler, effectively reducing the burst release effect and adverse reactions of the drug. The organic-inorganic composite porous antibacterial scaffold provides a good osteogenic environment and osteoconduction network effect for the drug-efficacy filler. The drug-efficacy filler can also directly enhance signaling pathways to further stimulate osteoblast growth. The two work synergistically to significantly enhance the osteogenic effect, achieving excellent bone repair effect and obtaining a bone growth-activating support implant material based on traditional Chinese medicine.

[0020] Preferably, in step S2, during the pretreatment process, freezing at -20°C for 3-4 hours is beneficial to the stability of the drug-efficacy filler adsorbed on the scaffold and reduces the burst release of the drug-efficacy filler.

[0021] The beneficial effects achieved by this invention are as follows:

[0022] This invention crosslinks and composites Co hollow spheres loaded with carbon nanotubes with sodium alginate, nano-hydroxyapatite, and transition metal carbide nanosheets to form an organic-inorganic composite porous antibacterial scaffold. This scaffold not only possesses excellent mechanical and antibacterial properties but also stably supports more drug-efficacy fillers and allows for their slow release. The drug-efficacy fillers further enhance the stability of the scaffold structure. The synergistic effect of both significantly enhances the antibacterial and osteogenic properties of the implanted material, achieving excellent bone repair results. In this organic-inorganic composite porous antibacterial scaffold, nano-hydroxyapatite is first inserted into transition metal carbide nanosheets... The interlayer spacing of nanosheets reduces the stacking of transition metal carbide nanosheets. Then, hollow Co spheres loaded with carbon nanotubes are used to fill these layers, followed by cross-linking with sodium alginate and calcium carbonate to form a composite gel structure. This structure exhibits continuous, dense, and porous characteristics, increasing the contact area with surrounding tissues, enhancing cell adhesion and signal transduction capabilities, and providing abundant adsorption sites. It can not only adhere to bacteria for excellent antibacterial performance but also load more drug components for slow and stable release. The interweaving of hollow spheres and nanosheets provides more stable support. The Co spheres loaded with carbon nanotubes... Hollow spheres, nano-hydroxyapatite, and transition metal carbide nanosheets can promote the attachment, proliferation, and differentiation of osteoblasts, thereby promoting new bone formation. The pharmacological filler, prepared as lyophilized powder and concentrated solution, ensures comprehensive and effective efficacy. It can promote the expression of osteogenic factors and multiple signaling pathways such as alkaline phosphatase, osteopontin, and osteocalcin, effectively activating osteoblast differentiation and proliferation. It also exerts broad-spectrum antibacterial activity. Loading it onto an organic-inorganic composite porous antibacterial scaffold further improves the scaffold's mechanical properties. The porous structure of the scaffold also increases the loading capacity and stability of the pharmacological filler. Qualitative analysis allows for slow and sustained release of the drug-efficacy filler, reducing burst release effects and adverse reactions. The organic-inorganic composite porous antibacterial scaffold provides a favorable osteogenic environment and osteoconductive network effect for the drug-efficacy filler, which is conducive to the more comprehensive and sufficient enhancement of signaling pathway expression, thereby further stimulating osteoblast growth. The synergistic effect of the two achieves excellent bone repair results. This invention uses an organic-inorganic composite porous antibacterial scaffold and drug-efficacy filler to create a traditional Chinese medicine-activated bone growth support implant material with excellent mechanical and antibacterial properties, enabling effective bone repair therapy. Attached Figure Description

[0023] Figure 1 This is a scanning electron microscope image of the organic-inorganic composite porous antibacterial scaffold prepared in Example 1 of the present invention;

[0024] Figure 2 The figures show the mechanical strength results of Examples 1-4 and Comparative Examples 1-3 of the present invention;

[0025] Figure 3These are the results of the inhibition zone diameters in Examples 1-4 and Comparative Examples 1-3 of the present invention;

[0026] Figure 4 The images show the cartilage repair results of Examples 1-4 and Comparative Examples 1-3 of the present invention. Detailed Implementation

[0027] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0029] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; unless otherwise specified, the experimental materials used in the following embodiments are all purchased from commercial channels.

[0030] Example 1

[0031] This embodiment proposes a bone growth-activating support implant material based on traditional Chinese medicine, comprising the following components by weight: 20 parts of organic-inorganic composite porous antibacterial scaffold and 30 parts of drug-efficacy filler.

[0032] The organic-inorganic composite porous antibacterial scaffold comprises the following components in parts by weight: 15 parts sodium alginate, 20 parts transition metal carbide nanosheets, 8 parts nano-hydroxyapatite, 30 parts Co hollow spheres loaded with carbon nanotubes, and 8 parts gluconolactone.

[0033] The medicinal filler contains the following components in parts by weight: Epimedium 5 parts, Dioscorea opposita 5 parts, Drynaria fortunei 5 parts, Astragalus membranaceus 5 parts, Deer antler glue 5 parts, Frankincense 5 parts, Cuscuta chinensis 5 parts, Myrrh 5 parts, Lycium barbarum 5 parts, Achyranthes bidentata 5 parts, Ligustrum lucidum 5 parts, Ostrea gigas 5 parts, Rehmannia glutinosa 5 parts.

[0034] The preparation method of the organic-inorganic composite porous antibacterial scaffold specifically includes the following steps:

[0035] (1) Add 3.0 g of lithium fluoride to 40 mL of 30% hydrochloric acid solution, and slowly add 2.0 g of titanium aluminum carbide while stirring at 60 rpm. After the addition is complete, stir at 40 °C for 36 h. Centrifuge the mixture at 4000 rpm for 10 min to remove the supernatant. Wash the precipitate 5 times with 10% dilute hydrochloric acid, and then repeatedly centrifuge and wash with deionized water until the pH is 6.0. Add the washed precipitate to 100 mL of deionized water and sonicate in an ice bath for 1 minute. h, the obtained colloidal solution was centrifuged at 5000 rpm for 20 min, the upper colloidal solution was taken and filtered into a thin film using a vacuum circulating water filter, dried, the transition metal carbide has high strength and flexibility, can withstand the mechanical stress in the bone repair process and provide necessary support. The transition metal carbide has antibacterial properties, which can reduce the risk of postoperative infection. The conductivity of the transition metal carbide can be used to apply electrical stimulation to promote osteoblast growth and bone tissue regeneration, improve the success rate of bone repair, and obtain transition metal carbide nanosheets;

[0036] (2) Dissolve 19.8g of sodium gluconate in 300mL of deionized water, then add cobalt nitrate hexahydrate (26.2g). The introduction of cobalt can reduce the adhesion rate of bacteria, giving it certain antibacterial properties and reducing the risk of bacterial infection and inflammation. Cobalt can promote the transformation of macrophages into the M2 phenotype, creating an immune environment conducive to bone regeneration. It can also promote the differentiation of osteoblasts, activate multiple signaling pathways related to bone resorption and bone formation, and accelerate the formation of new bone. Stir well, turn on the preheating furnace, and raise the temperature to 80°C at a rate of 10°C / min. After reaching 0℃, the solution is transferred to an ultrasonic nebulizer. The ultrasonic device is turned on and nitrogen gas is introduced at a rate of 1.5 L / min. The nitrogen gas can blow the product into a collection bottle filled with ethanol. The black solid is collected, filtered and washed 5 times with deionized water, and then vacuum dried. The hollow structure formed by the aggregation of Co nanoparticles reduces the weight of the implant material, reduces the pressure on the surrounding tissue, and can also provide sufficient mechanical strength and excellent elasticity, which can withstand greater pressure and effectively reduce wear and damage. The porous nature of the hollow spheres is conducive to bone cell growth and angiogenesis, promoting new bone formation, thus obtaining Co hollow spheres.

[0037] (3) The Co hollow spheres described in step (2) are placed in a tube furnace and heated to 700°C at a heating rate of 10°C / min under an argon atmosphere of 80 mL / min. Then, a mixture of acetylene and hydrogen is introduced at a rate of 80 mL / min and kept at the temperature for 40 min. The acetylene and hydrogen are then stopped and the temperature is lowered to room temperature under argon protection. Using acetylene as a carbon source, dense carbon nanotubes are grown in situ on the surface of the Co hollow spheres under the reducing effect of hydrogen. This effectively prevents the accumulation and aggregation of hollow spheres and increases the contact area. The spheres have more active sites, which can adsorb active substances and achieve sustained release, thus improving the stability and effectiveness of active substances. This is beneficial for better stimulating bone growth and bone repair, resulting in Co hollow spheres loaded with carbon nanotubes.

[0038] (4) Disperse the transition metal carbide nanosheets and nano hydroxyapatite described in step (1) in 50 mL of deionized water, sonicate for 2 h, centrifuge, freeze dry the precipitate first, then mix it evenly with the Co hollow spheres loaded with carbon nanotubes described in step (3), and then anneal it in a nitrogen environment at 400 °C for 2 h. The nano hydroxyapatite is first inserted into the interlayer spacing of the transition metal carbide nanosheets, which reduces the stacking of nanosheets and provides conditions for the subsequent filling of the Co hollow spheres loaded with carbon nanotubes. This further increases the specific surface area of ​​the material and the continuity and density of the network structure, which is conducive to loading more active substances and playing a more stable supporting role, thus obtaining the composite material.

[0039] (5) Disperse the composite material described in step (4) in 50 mL of deionized water, sonicate for 2 h, add 1.5 g of sodium alginate, and magnetically stir for 30 min to obtain the liquid for later use. Weigh 0.3 g of calcium carbonate and add it to 5 mL of deionized water, sonicate for 30 min, and then add the calcium carbonate suspension to the liquid for later use at 2000 rpm. After dispersing evenly, add gluconolactone. The amount of gluconolactone added is 0.8 g. The weakly acidic environment formed by the hydrolysis of gluconolactone promotes the release of calcium ions from calcium carbonate to crosslink and form a gel. Gluconolactone can reduce the inflammatory response during bone repair, stimulate angiogenesis, and improve local blood supply. This process provides more nutrients and oxygen for bone repair, stimulates osteoblast proliferation and differentiation, and accelerates bone matrix synthesis, thereby promoting new bone formation. After thorough mixing, the mixture is transferred to a 24-well plate and reacted at 4°C for 24 hours. Then, it is freeze-dried under vacuum at -80°C for 48 hours. Through the cross-linking of organic and inorganic materials, a complex, continuous, dense, and porous structure is formed, exhibiting excellent antibacterial and mechanical properties. It provides more stable support and has abundant adsorption sites, allowing for the loading of more drug components to achieve slow and stable release, reducing the occurrence of burst release effects. This results in a dual bone growth and bone repair effect of both the drug and the scaffold, yielding an organic-inorganic composite porous antibacterial scaffold.

[0040] This embodiment provides a method for preparing a bone growth-activating support implant material made from traditional Chinese medicine, specifically including the following steps:

[0041] S1. Place Epimedium, Dioscorea opposita, Drynaria fortunei, Astragalus membranaceus, Cervi cornu colla, Boswellia carterii, Cuscuta chinensis, Commiphora myrrha, Lycium barbarum, Achyranthes bidentata, Ligustrum lucidum, Ostrea gigas, and Rehmannia glutinosa in a decoction machine with 15 times the amount of water and soak for 3 hours. Decoction twice, extract by gentle boiling for 3 hours. Combine the decoctions, freeze-dry the residue for later use. Concentrate the collected filtrate to 1 / 5 of the original volume under vacuum pressure -0.06 MPa and temperature 50℃. Then pour the freeze-dried residue powder into the concentrated liquid, sonicate for 40 minutes, and magnetically stir for 2 hours. The synergistic use of Chinese herbal components can promote the expression of osteogenic related factors (such as alkaline phosphatase, osteopontin, and osteocalcin) and activate multiple signaling pathways, thereby effectively activating the differentiation and proliferation of osteoblasts. It can also adsorb onto the bacterial surface to prevent the absorption of nutrients or enter the bacteria to produce flocculation and thus produce antibacterial effects. Its antibacterial spectrum is relatively broad. At the same time, the form of freeze-dried powder and concentrated liquid ensures the comprehensiveness and effectiveness of the efficacy, resulting in a medicinal filler.

[0042] S2. Immerse the organic-inorganic composite porous antibacterial scaffold in the medicated filler material described in step S1 for 3 hours. Remove and pre-treat by freezing at -20°C for 4 hours. This improves the stability of the initially added medicated filler material adsorbed onto the scaffold and reduces the burst release of the filler. Then, use a dropper to add the remaining medicated filler material drop by drop, allowing it to stand for 50 seconds after each addition. This immersion and drop-in method promotes the uniformity and stability of the medicated filler. After addition, freeze-dry at -80°C for 36 hours, then place it in a clean bench for UV irradiation for 8 hours for sterilization. The medicated filler material loaded onto the organic-inorganic composite porous antibacterial scaffold improves the scaffold's performance. The pharmacologically active filler exhibits excellent mechanical properties and stability. It can induce osteoblasts to secrete extracellular matrix to establish a connection network, further enhancing the strength of the scaffold and its surrounding area. At the same time, the porous structure of the scaffold improves drug loading capacity and drug loading stability, enabling the pharmacologically active filler to achieve slow and continuous release, effectively reducing the burst release effect of drugs and the occurrence of adverse reactions. The organic-inorganic composite porous antibacterial scaffold provides a good osteogenic environment and osteoconductive network effect for the pharmacologically active filler. The pharmacologically active filler can also directly enhance signaling pathways to further stimulate osteoblast growth. The two work synergistically to significantly enhance the osteogenic effect, achieving excellent bone repair effect and obtaining a bone growth-activating support implant material based on traditional Chinese medicine.

[0043] In this embodiment, the microstructure of the prepared organic-inorganic composite porous antibacterial scaffold was observed using scanning electron microscopy. Figure 1 This is a 10,000x magnified SEM image of the organic-inorganic composite porous antibacterial scaffold prepared in Example 1, as shown below. Figure 1 The organic-inorganic composite porous antibacterial scaffold prepared in this embodiment exhibits a dense porous structure.

[0044] Example 2

[0045] This embodiment proposes a bone growth-activating support implant material based on traditional Chinese medicine, comprising the following components by weight: 10 parts of an organic-inorganic composite porous antibacterial scaffold and 20 parts of a drug-efficacy filler.

[0046] The organic-inorganic composite porous antibacterial scaffold comprises the following components in parts by weight: 10 parts sodium alginate, 10 parts transition metal carbide nanosheets, 5 parts nano hydroxyapatite, 20 parts Co hollow spheres loaded with carbon nanotubes, and 6 parts gluconolactone.

[0047] The medicinal filler contains the following components in parts by weight: Epimedium 3 parts, Dioscorea opposita 3 parts, Drynaria fortunei 3 parts, Astragalus membranaceus 3 parts, Deer antler glue 3 parts, Frankincense 3 parts, Cuscuta chinensis 3 parts, Myrrh 3 parts, Lycium barbarum 3 parts, Achyranthes bidentata 3 parts, Ligustrum lucidum 3 parts, Ostrea gigas 3 parts, Rehmannia glutinosa 3 parts.

[0048] The preparation method of the organic-inorganic composite porous antibacterial scaffold specifically includes the following steps:

[0049] (1) Add 2.0g of lithium fluoride to 40mL of 30% hydrochloric acid solution, and slowly add 1.0g of titanium aluminum carbide while stirring at 50rpm. After the addition is complete, stir at 30℃ for 24h. Centrifuge the mixture at 2000rpm for 5min to remove the supernatant. Wash the precipitate three times with 10% dilute hydrochloric acid, and then repeatedly centrifuge and wash with deionized water until the pH is 6.0. Add the washed precipitate to 100mL of deionized water and sonicate in an ice bath for 0. After 5 hours, the obtained colloidal solution was centrifuged at 4000 rpm for 10 minutes. The upper colloidal solution was then filtered into a thin film using a vacuum circulating water filter and dried. Transition metal carbides possess high strength and flexibility, enabling them to withstand mechanical stress during bone repair and provide necessary support. Transition metal carbides also have antibacterial properties, which can reduce the risk of postoperative infection. Furthermore, the conductivity of transition metal carbides can be used to apply electrical stimulation, promoting osteoblast growth and bone tissue regeneration, thereby improving the success rate of bone repair. This process yields transition metal carbide nanosheets.

[0050] (2) Dissolve 19.8g of sodium gluconate in 300mL of deionized water, then add cobalt nitrate hexahydrate (24.2g). The introduction of cobalt can reduce the adhesion rate of bacteria, giving it certain antibacterial properties and reducing the risk of bacterial infection and inflammation. Cobalt can promote the transformation of macrophages into the M2 phenotype, creating an immune environment conducive to bone regeneration. It can also promote the differentiation of osteoblasts, activate multiple signaling pathways related to bone resorption and bone formation, and accelerate the formation of new bone. Stir well, turn on the preheating furnace, and raise the temperature to 70°C at a rate of 10°C / min. After reaching 0℃, the solution is transferred to an ultrasonic nebulizer. The ultrasonic device is turned on and nitrogen gas is introduced at a rate of 1.5 L / min. The nitrogen gas can blow the product into a collection bottle filled with ethanol. The black solid is collected, filtered and washed three times with deionized water, and then vacuum dried. The hollow structure formed by the aggregation of Co nanoparticles reduces the weight of the implant material, reduces the pressure on the surrounding tissue, and can also provide sufficient mechanical strength and excellent elasticity, which can withstand greater pressure and effectively reduce wear and damage. The porous nature of the hollow spheres is conducive to bone cell growth and angiogenesis, promoting new bone formation, thus obtaining Co hollow spheres.

[0051] (3) Place the Co hollow spheres described in step (2) in a tube furnace, raise the temperature to 700°C at a rate of 8°C / min under an argon atmosphere of 80 mL / min, and then introduce a mixture of acetylene and hydrogen at a rate of 80 mL / min. Keep the temperature for 20 min, stop introducing acetylene and hydrogen, and lower the temperature to room temperature under argon protection. Using acetylene as a carbon source, under the reducing effect of hydrogen, dense carbon nanotubes grow in situ on the surface of the Co hollow spheres, effectively preventing the accumulation and aggregation of hollow spheres, increasing the contact area, having more active sites, adsorbing active substances and achieving sustained release, improving the stability and effectiveness of active substances, and facilitating better stimulation of bone growth and bone repair, thus obtaining Co hollow spheres loaded with carbon nanotubes.

[0052] (4) Disperse the transition metal carbide nanosheets and nano hydroxyapatite described in step (1) in 50 mL of deionized water, sonicate for 1 h, centrifuge, freeze dry the precipitate first, and then mix it evenly with the Co hollow spheres loaded with carbon nanotubes described in step (3). Then anneal it in a nitrogen environment at 350 °C for 1 h. The nano hydroxyapatite is first inserted into the interlayer spacing of the transition metal carbide nanosheets, which reduces the stacking of nanosheets and provides conditions for the subsequent filling of the Co hollow spheres loaded with carbon nanotubes. This further increases the specific surface area of ​​the material and the continuity and density of the network structure, which is conducive to loading more active substances and playing a more stable supporting role, thus obtaining a composite material.

[0053] (5) Disperse the composite material described in step (4) in 50 mL of deionized water, sonicate for 1 h, add 1.0 g of sodium alginate, and magnetically stir for 20 min to obtain the liquid for later use. Weigh 0.2 g of calcium carbonate and add it to 5 mL of deionized water, sonicate for 20 min, and then add the calcium carbonate suspension to the liquid for later use at 1000 rpm. After dispersing evenly, add gluconolactone. The amount of gluconolactone added is 0.6 g. The weakly acidic environment formed by the hydrolysis of gluconolactone promotes the release of calcium ions from calcium carbonate to crosslink and form a gel. Gluconolactone can reduce the inflammatory response during bone repair, stimulate angiogenesis, and improve local blood supply. This process provides more nutrients and oxygen for bone repair, stimulates osteoblast proliferation and differentiation, and accelerates bone matrix synthesis, thereby promoting new bone formation. After thorough mixing, the mixture is transferred to a 24-well plate and reacted at 4°C for 12 hours. Then, it is freeze-dried under vacuum at -80°C for 36 hours. Through the cross-linking of organic and inorganic materials, a complex, continuous, dense, and porous structure is formed, exhibiting excellent antibacterial and mechanical properties. It provides more stable support and has abundant adsorption sites, allowing for the loading of more drug components to achieve slow and stable release, reducing the occurrence of burst release effects. This process exerts the dual effects of drug and scaffold in promoting bone growth and bone repair, resulting in an organic-inorganic composite porous antibacterial scaffold.

[0054] This embodiment provides a method for preparing a bone growth-activating support implant material made from traditional Chinese medicine, specifically including the following steps:

[0055] S1. Place Epimedium, Dioscorea opposita, Drynaria fortunei, Astragalus membranaceus, Cervi cornu colla, Boswellia carterii, Cuscuta chinensis, Commiphora myrrha, Lycium barbarum, Achyranthes bidentata, Ligustrum lucidum, Ostrea gigas, and Rehmannia glutinosa in a decoction machine with 10 times the amount of water and soak for 2 hours. Decoction once, extract by gentle boiling for 2 hours. Combine the decoctions, freeze-dry the residue for later use. Concentrate the collected filtrate to 1 / 6 of the original volume under vacuum pressure -0.06 MPa and temperature 40℃. Then pour the freeze-dried residue powder into the concentrate, sonicate for 30 minutes, and magnetically stir for 1 hour. The synergistic use of Chinese herbal ingredients can promote the expression of osteogenic related factors (such as alkaline phosphatase, osteopontin, and osteocalcin) and activate multiple signaling pathways, thereby effectively activating the differentiation and proliferation of osteoblasts. It can also adsorb onto the bacterial surface to prevent the absorption of nutrients or enter the bacteria to produce flocculation and thus produce antibacterial effects. Its antibacterial spectrum is relatively broad. At the same time, the form of freeze-dried powder and concentrate ensures the comprehensiveness and effectiveness of the efficacy, resulting in a medicinal filler.

[0056] S2. Immerse the organic-inorganic composite porous antibacterial scaffold in the medicated filler material described in step S1 for 2 hours. Remove and pre-treat by freezing at -20°C for 3 hours. This improves the stability of the initially added medicated filler material adsorbed onto the scaffold and reduces the burst release of the filler. Then, use a dropper to add the remaining medicated filler material drop by drop, allowing it to stand for 30 seconds after each addition. This immersion and drop-in method promotes the uniformity and stability of the medicated filler. After addition, freeze-dry at -80°C for 24 hours, then place it in a clean bench for UV irradiation for 8 hours for sterilization. The medicated filler material loaded onto the organic-inorganic composite porous antibacterial scaffold improves the scaffold's performance. The pharmacologically active filler exhibits excellent mechanical properties and stability. It can induce osteoblasts to secrete extracellular matrix to establish a connection network, further enhancing the strength of the scaffold and its surrounding area. At the same time, the porous structure of the scaffold improves drug loading capacity and drug loading stability, enabling the pharmacologically active filler to achieve slow and continuous release, effectively reducing the burst release effect of drugs and the occurrence of adverse reactions. The organic-inorganic composite porous antibacterial scaffold provides a good osteogenic environment and osteoconductive network effect for the pharmacologically active filler. The pharmacologically active filler can also directly enhance signaling pathways to further stimulate osteoblast growth. The two work synergistically to significantly enhance the osteogenic effect, achieving excellent bone repair effect and obtaining a bone growth-activating support implant material based on traditional Chinese medicine.

[0057] Example 3

[0058] This embodiment proposes a bone growth-activating support implant material based on traditional Chinese medicine, comprising the following components by weight: 15 parts of an organic-inorganic composite porous antibacterial scaffold and 25 parts of a drug-efficacy filler.

[0059] The organic-inorganic composite porous antibacterial scaffold comprises the following components in parts by weight: 12.5 parts sodium alginate, 15 parts transition metal carbide nanosheets, 6.5 parts nano hydroxyapatite, 25 parts Co hollow spheres loaded with carbon nanotubes, and 7 parts gluconolactone.

[0060] The medicinal filler contains the following components in parts by weight: Epimedium 4 parts, Dioscorea opposita 4 parts, Drynaria fortunei 4 parts, Astragalus membranaceus 4 parts, Deer antler glue 4 parts, Frankincense 4 parts, Cuscuta chinensis 4 parts, Myrrh 4 parts, Lycium barbarum 4 parts, Achyranthes bidentata 4 parts, Ligustrum lucidum 4 parts, Ostrea gigas 4 parts, Rehmannia glutinosa 4 parts.

[0061] The preparation method of the organic-inorganic composite porous antibacterial scaffold specifically includes the following steps:

[0062] (1) Add 2.5g of lithium fluoride to 40mL of 30% hydrochloric acid solution, stir at 55rpm and slowly add 1.5g of titanium aluminum carbide. After the addition is complete, stir at 35℃ for 30h. Centrifuge the mixture at 3000rpm for 7.5min to remove the supernatant. Wash the precipitate 4 times with 10% dilute hydrochloric acid, and then repeatedly centrifuge and wash with deionized water until the pH is 6.0. Add the washed precipitate to 100mL of deionized water and sonicate in an ice bath for 0. After 75 hours, the obtained colloidal solution was centrifuged at 4500 rpm for 15 minutes. The upper colloidal solution was then filtered into a thin film using a vacuum circulating water filter and dried. The transition metal carbide has high strength and flexibility, which can withstand the mechanical stress during the bone repair process and provide necessary support. The transition metal carbide has antibacterial properties, which can reduce the risk of postoperative infection. The conductivity of the transition metal carbide can be used to apply electrical stimulation to promote osteoblast growth and bone tissue regeneration, thereby improving the success rate of bone repair. The resulting transition metal carbide nanosheets were obtained.

[0063] (2) Dissolve 19.8g of sodium gluconate in 300mL of deionized water, then add 25.2g of cobalt nitrate hexahydrate. The introduction of cobalt can reduce the adhesion rate of bacteria, giving it certain antibacterial properties and reducing the risk of bacterial infection and inflammation. Cobalt can promote the transformation of macrophages into the M2 phenotype, creating an immune environment conducive to bone regeneration. It can also promote the differentiation of osteoblasts, activate multiple signaling pathways related to bone resorption and bone formation, and accelerate the formation of new bone. Stir well, turn on the preheating furnace, and raise the temperature to 75°C at a rate of 10°C / min. After reaching 0℃, the solution is transferred to an ultrasonic nebulizer. The ultrasonic device is turned on and nitrogen gas is introduced at a rate of 1.5 L / min. The nitrogen gas can blow the product into a collection bottle filled with ethanol. The black solid is collected, filtered and washed four times with deionized water, and then vacuum dried. The hollow structure formed by the aggregation of Co nanoparticles reduces the weight of the implant material, reduces the pressure on the surrounding tissue, and can also provide sufficient mechanical strength and excellent elasticity, which can withstand greater pressure and effectively reduce wear and damage. The porous nature of the hollow spheres is conducive to bone cell growth and angiogenesis, promoting new bone formation, thus obtaining Co hollow spheres.

[0064] (3) Place the Co hollow spheres described in step (2) in a tube furnace, raise the temperature to 700°C at a rate of 9°C / min under an argon atmosphere of 80 mL / min, and then introduce a mixture of acetylene and hydrogen at a rate of 80 mL / min. Keep the temperature for 30 min, stop introducing acetylene and hydrogen, and lower the temperature to room temperature under argon protection. Using acetylene as a carbon source, under the reduction of hydrogen, dense carbon nanotubes grow in situ on the surface of the Co hollow spheres, effectively preventing the accumulation and aggregation of hollow spheres, increasing the contact area, having more active sites, adsorbing active substances and achieving sustained release, improving the stability and effectiveness of active substances, and facilitating better stimulation of bone growth and bone repair, thus obtaining Co hollow spheres loaded with carbon nanotubes.

[0065] (4) Disperse the transition metal carbide nanosheets and nano hydroxyapatite described in step (1) in 50 mL of deionized water, sonicate for 1.5 h, centrifuge, freeze dry the precipitate, mix it evenly with the Co hollow spheres loaded with carbon nanotubes described in step (3), and then anneal it in a nitrogen environment at 375 °C for 1.5 h. The nano hydroxyapatite is first inserted into the interlayer spacing of the transition metal carbide nanosheets, which reduces the stacking of nanosheets and provides conditions for the subsequent filling of the Co hollow spheres loaded with carbon nanotubes. This further increases the specific surface area of ​​the material and the continuity and density of the network structure, which is conducive to loading more active substances and playing a more stable supporting role, thus obtaining a composite material.

[0066] (5) Disperse the composite material described in step (4) in 50 mL of deionized water, sonicate for 1.5 h, add 1.25 g of sodium alginate, and magnetically stir for 25 min to obtain the liquid for later use. Weigh 0.25 g of calcium carbonate and add it to 5 mL of deionized water, sonicate for 25 min, and then add the calcium carbonate suspension to the liquid for later use at 1500 rpm. After dispersing evenly, add gluconolactone. The amount of gluconolactone added is 0.7 g. The weakly acidic environment formed by the hydrolysis of gluconolactone promotes the release of calcium ions from calcium carbonate to crosslink and form a gel. Gluconolactone can reduce the inflammatory response during bone repair, stimulate angiogenesis, and improve local blood circulation. The solution provides more nutrients and oxygen for bone repair, stimulates osteoblast proliferation and differentiation, accelerates bone matrix synthesis, and thus promotes new bone formation. After thorough mixing, the solution is transferred to a 24-well plate and reacted at 4°C for 18 hours. Then, it is freeze-dried under vacuum at -80°C for 42 hours. Through the cross-linking of organic and inorganic materials, a complex, continuous, dense, and porous structure is formed, which has excellent antibacterial and mechanical properties. It can provide more stable support and has abundant adsorption sites, allowing for the loading of more drug components to achieve slow and stable release, reducing the occurrence of burst release effects. It exerts the dual bone growth and bone repair effects of both drugs and scaffolds, resulting in an organic-inorganic composite porous antibacterial scaffold.

[0067] This embodiment provides a method for preparing a bone growth-activating support implant material made from traditional Chinese medicine, specifically including the following steps:

[0068] S1. Place Epimedium, Dioscorea opposita, Drynaria fortunei, Astragalus membranaceus, Cervi cornu colla, Boswellia carterii, Cuscuta chinensis, Commiphora myrrha, Lycium barbarum, Achyranthes bidentata, Ligustrum lucidum, Ostrea gigas, and Rehmannia glutinosa in a decoction machine with 12.5 times the amount of water and soak for 2 hours. Decoction once, extract by gentle boiling for 2.5 hours. Combine the decoctions, freeze-dry the residue for later use. Concentrate the collected filtrate to 1 / 5 of the original volume under vacuum pressure -0.06 MPa and temperature 45℃. Then pour the freeze-dried residue powder into the concentrate, sonicate for 35 minutes, and magnetically stir for 1.5 hours. The synergistic use of Chinese herbal components can promote the expression of osteogenic related factors (such as alkaline phosphatase, osteopontin, and osteocalcin) and activate multiple signaling pathways, thereby effectively activating the differentiation and proliferation of osteoblasts. It can also adsorb onto the bacterial surface to prevent the absorption of nutrients or enter the bacteria to produce flocculation and thus produce antibacterial effects. Its antibacterial spectrum is relatively broad. At the same time, the form of freeze-dried powder and concentrate ensures the comprehensiveness and effectiveness of the efficacy, resulting in a medicinal filler.

[0069] S2. Immerse the organic-inorganic composite porous antibacterial scaffold in the medicated filler material described in step S1 for 2.5 hours. Remove and pre-treat by freezing at -20°C for 3.5 hours. This improves the stability of the initially added medicated filler material adsorbed onto the scaffold and reduces sudden release. Then, use a dropper to add the remaining medicated filler material drop by drop, allowing it to stand for 40 seconds after each addition. This immersion and drop-in method promotes the uniformity and stability of the medicated filler material. After addition, freeze-dry at -80°C for 30 hours, then place it in a clean bench for UV irradiation for 8 hours for sterilization. The medicated filler material loaded onto the organic-inorganic composite porous antibacterial scaffold improves the scaffold's stability. The mechanical properties and stability of the scaffold are improved. The pharmacologically active filler can induce osteoblasts to secrete extracellular matrix to establish a connection network, further enhancing the strength of the scaffold and its surrounding area. At the same time, the porous structure of the scaffold increases the drug loading capacity and drug loading stability, enabling the pharmacologically active filler to achieve slow and continuous release, effectively reducing the burst release effect of drugs and the occurrence of adverse reactions. The organic-inorganic composite porous antibacterial scaffold provides a good osteogenic environment and osteoconduction network effect for the pharmacologically active filler. The pharmacologically active filler can also directly enhance the signaling pathway to further stimulate osteoblast growth. The two work synergistically to significantly enhance the osteogenic effect, obtain excellent bone repair effect, and obtain a bone growth-activating support implant material of traditional Chinese medicine.

[0070] Example 4

[0071] This embodiment proposes a bone growth-activating support implant material based on traditional Chinese medicine, comprising the following components by weight: 20 parts of an organic-inorganic composite porous antibacterial scaffold and 20 parts of a drug-efficacy filler.

[0072] The organic-inorganic composite porous antibacterial scaffold comprises the following components in parts by weight: 15 parts sodium alginate, 20 parts transition metal carbide nanosheets, 5 parts nano hydroxyapatite, 20 parts Co hollow spheres loaded with carbon nanotubes, and 6 parts gluconolactone.

[0073] The medicinal filler contains the following components in parts by weight: Epimedium 5 parts, Dioscorea opposita 5 parts, Drynaria fortunei 5 parts, Astragalus membranaceus 5 parts, Cervi cornu colla 5 parts, Boswellia carterii 5 parts, Cuscuta chinensis 5 parts, Commiphora myrrha 3 parts, Lycium barbarum 3 parts, Achyranthes bidentata 3 parts, Ligustrum lucidum 3 parts, Ostrea gigas 3 parts, Rehmannia glutinosa 3 parts.

[0074] The preparation method of the organic-inorganic composite porous antibacterial scaffold specifically includes the following steps:

[0075] (1) Add 3.0g of lithium fluoride to 40mL of 30% hydrochloric acid solution, stir at 60rpm and slowly add 2.0g of titanium aluminum carbide. After the addition is complete, stir at 40℃ for 24h. Centrifuge the mixture at 4000rpm for 5min to remove the supernatant. Wash the precipitate 5 times with 10% dilute hydrochloric acid, and then repeatedly centrifuge and wash with deionized water until the pH is 6.0. Add the washed precipitate to 100mL of deionized water and sonicate in an ice bath for 0. After 5 hours, the obtained colloidal solution was centrifuged at 5000 rpm for 10 minutes. The upper colloidal solution was then filtered into a thin film using a vacuum circulating water filter and dried. Transition metal carbides possess high strength and flexibility, enabling them to withstand mechanical stress during bone repair and provide necessary support. Transition metal carbides also have antibacterial properties, which can reduce the risk of postoperative infection. Furthermore, the conductivity of transition metal carbides can be used to apply electrical stimulation, promoting osteoblast growth and bone tissue regeneration, thereby improving the success rate of bone repair. This process yields transition metal carbide nanosheets.

[0076] (2) Dissolve 19.8g of sodium gluconate in 300mL of deionized water, then add cobalt nitrate hexahydrate (24.2g). The introduction of cobalt can reduce the adhesion rate of bacteria, giving it certain antibacterial properties and reducing the risk of bacterial infection and inflammation. Cobalt can promote the transformation of macrophages into the M2 phenotype, creating an immune environment conducive to bone regeneration. It can also promote the differentiation of osteoblasts, activate multiple signaling pathways related to bone resorption and bone formation, and accelerate the formation of new bone. Stir well, turn on the preheating furnace, and raise the temperature to 80°C at a rate of 10°C / min. After reaching 0℃, the solution is transferred to an ultrasonic nebulizer. The ultrasonic device is turned on and nitrogen gas is introduced at a rate of 1.5 L / min. The nitrogen gas can blow the product into a collection bottle filled with ethanol. The black solid is collected, filtered and washed 5 times with deionized water, and then vacuum dried. The hollow structure formed by the aggregation of Co nanoparticles reduces the weight of the implant material, reduces the pressure on the surrounding tissue, and can also provide sufficient mechanical strength and excellent elasticity, which can withstand greater pressure and effectively reduce wear and damage. The porous nature of the hollow spheres is conducive to bone cell growth and angiogenesis, promoting new bone formation, thus obtaining Co hollow spheres.

[0077] (3) Place the Co hollow spheres described in step (2) in a tube furnace, raise the temperature to 700°C at a rate of 10°C / min under an argon atmosphere of 80 mL / min, and then introduce a mixture of acetylene and hydrogen at a rate of 80 mL / min. Keep the temperature for 20 min, stop introducing acetylene and hydrogen, and lower the temperature to room temperature under argon protection. Using acetylene as a carbon source, under the reducing effect of hydrogen, dense carbon nanotubes grow in situ on the surface of the Co hollow spheres, effectively preventing the accumulation and aggregation of hollow spheres, increasing the contact area, having more active sites, adsorbing active substances and achieving sustained release, improving the stability and effectiveness of active substances, and facilitating better stimulation of bone growth and bone repair, thus obtaining Co hollow spheres loaded with carbon nanotubes.

[0078] (4) Disperse the transition metal carbide nanosheets and nano hydroxyapatite described in step (1) in 50 mL of deionized water, sonicate for 1 h, centrifuge, freeze dry the precipitate first, then mix it evenly with the Co hollow spheres loaded with carbon nanotubes described in step (3), and then anneal it in a nitrogen environment at 400 °C for 1 h. The nano hydroxyapatite is first inserted into the interlayer spacing of the transition metal carbide nanosheets, which reduces the stacking of nanosheets and provides conditions for the subsequent filling of the Co hollow spheres loaded with carbon nanotubes. This further increases the specific surface area of ​​the material and the continuity and density of the network structure, which is conducive to loading more active substances and playing a more stable supporting role, thus obtaining a composite material.

[0079] (5) Disperse the composite material described in step (4) in 50 mL of deionized water, sonicate for 1 h, add 1.5 g of sodium alginate, and magnetically stir for 20 min to obtain the liquid for later use. Weigh 0.2 g of calcium carbonate and add it to 5 mL of deionized water, sonicate for 20-30 min, and then add the calcium carbonate suspension to the liquid for later use at 2000 rpm. After dispersing evenly, add gluconolactone. The amount of gluconolactone added is 0.6 g. The weakly acidic environment formed by the hydrolysis of gluconolactone promotes the release of calcium ions from calcium carbonate to crosslink and form a gel. Gluconolactone can reduce the inflammatory response during bone repair, stimulate angiogenesis, and improve local blood supply. The reaction process provides more nutrients and oxygen for bone repair, stimulates osteoblast proliferation and differentiation, and accelerates bone matrix synthesis, thereby promoting new bone formation. After thorough mixing, the mixture is transferred to a 24-well plate and reacted at 4°C for 12 hours, followed by vacuum freeze-drying at -80°C for 36 hours. Through cross-linking of organic and inorganic materials, a complex, continuous, dense, and porous structure is formed, exhibiting excellent antibacterial and mechanical properties. It provides more stable support and has abundant adsorption sites, allowing for the loading of more drug components to achieve slow and stable release, reducing burst release effects. This results in a dual bone growth and repair effect of both the drug and the scaffold, yielding an organic-inorganic composite porous antibacterial scaffold.

[0080] This embodiment provides a method for preparing a bone growth-activating support implant material made from traditional Chinese medicine, specifically including the following steps:

[0081] S1. Place Epimedium, Dioscorea opposita, Drynaria fortunei, Astragalus membranaceus, Cervi cornu colla, Boswellia carterii, Cuscuta chinensis, Commiphora myrrha, Lycium barbarum, Achyranthes bidentata, Ligustrum lucidum, Ostrea gigas, and Rehmannia glutinosa in a decoction machine with 15 times the amount of water and soak for 2 hours. Decoction twice, extract by gentle boiling for 2 hours. Combine the decoctions, freeze-dry the residue for later use. Concentrate the collected filtrate to 1 / 6 of its original volume under vacuum pressure -0.06 MPa and temperature 50℃. Then pour the freeze-dried residue powder into the concentrate, sonicate for 30 minutes, and magnetically stir for 1 hour. The synergistic use of Chinese herbal ingredients can promote the expression of osteogenic related factors (such as alkaline phosphatase, osteopontin, and osteocalcin) and activate multiple signaling pathways, thereby effectively activating the differentiation and proliferation of osteoblasts. It can also adsorb onto the bacterial surface to prevent the absorption of nutrients or enter the bacteria to produce flocculation and thus produce antibacterial effects. Its antibacterial spectrum is relatively broad. At the same time, the form of freeze-dried powder and concentrate ensures the comprehensiveness and effectiveness of the efficacy, resulting in a medicinal filler.

[0082] S2. Immerse the organic-inorganic composite porous antibacterial scaffold in the medicated filler material described in step S1 for 2 hours. Remove and pre-treat by freezing at -20°C for 3 hours. This improves the stability of the initially added medicated filler material adsorbed onto the scaffold and reduces the burst release of the filler. Then, use a dropper to add the remaining medicated filler material drop by drop, allowing it to stand for 30 seconds after each addition. This immersion and drop-in method promotes the uniformity and stability of the medicated filler. After addition, freeze-dry at -80°C for 24 hours, then place it in a clean bench for UV irradiation for 8 hours for sterilization. The medicated filler material loaded onto the organic-inorganic composite porous antibacterial scaffold improves the scaffold's performance. The pharmacologically active filler exhibits excellent mechanical properties and stability. It can induce osteoblasts to secrete extracellular matrix to establish a connection network, further enhancing the strength of the scaffold and its surrounding area. At the same time, the porous structure of the scaffold improves drug loading capacity and drug loading stability, enabling the pharmacologically active filler to achieve slow and continuous release, effectively reducing the burst release effect of drugs and the occurrence of adverse reactions. The organic-inorganic composite porous antibacterial scaffold provides a good osteogenic environment and osteoconductive network effect for the pharmacologically active filler. The pharmacologically active filler can also directly enhance signaling pathways to further stimulate osteoblast growth. The two work synergistically to significantly enhance the osteogenic effect, achieving excellent bone repair effect and obtaining a bone growth-activating support implant material based on traditional Chinese medicine.

[0083] Comparative Example 1

[0084] This comparative example provides a bone growth-activating support implant material based on traditional Chinese medicine activity. The difference between this material and Example 1 is that the organic-inorganic composite porous antibacterial scaffold does not contain Co hollow spheres loaded with carbon nanotubes; the preparation method of the organic-inorganic composite porous antibacterial scaffold does not include steps (2) and (3); the preparation method of the bone growth-activating support implant material based on traditional Chinese medicine activity is the same as that of Example 1.

[0085] Comparative Example 2

[0086] This comparative example provides a bone growth-activating support implant material based on traditional Chinese medicine activity. The difference between this material and Example 1 is that the organic-inorganic composite porous antibacterial scaffold does not contain transition metal carbide nanosheets or nano-hydroxyapatite; the preparation method of the organic-inorganic composite porous antibacterial scaffold does not include steps (1) and (4); the preparation method of the bone growth-activating support implant material based on traditional Chinese medicine activity is the same as that of Example 1.

[0087] Comparative Example 3

[0088] This comparative example provides a herbal active bone growth-activating support implant material, which differs from Example 1 in that the herbal active bone growth-activating support implant material does not contain pharmacological fillers; the preparation method of the organic-inorganic composite porous antibacterial scaffold is the same as that of Example 1; the preparation method of the herbal active bone growth-activating support implant material does not include step S1.

[0089] Experimental Example 1

[0090] Mechanical property test

[0091] Test samples: Traditional Chinese medicine active bone growth-activating support implant materials prepared in Examples 1-4 and Comparative Examples 1-3.

[0092] Test method: The test samples were subjected to compression tests using an electronic universal testing machine. A 100N sensor was used for the compression test, the compression rate was 5 mm / min, and the samples were compressed to 50% strain. In the compression test, 10 cycles of loading and unloading were performed, and the compression strain was kept constant at 40%. Three parallel tests were set up for each group of samples and the average value was taken.

[0093] Figure 2 The figures show the mechanical strength results of Examples 1-4 and Comparative Examples 1-3. As shown, the mechanical strength of Examples 1-4 is 9.5-10.8 MPa, indicating good mechanical properties; the mechanical strength of Comparative Examples 1-3 is 5.3-7.9 MPa, indicating poor mechanical properties. The organic-inorganic composite porous antibacterial scaffold of Comparative Example 1 does not contain Co hollow spheres loaded with carbon nanotubes, thus failing to fill and interweave transition metal carbide nanosheets, resulting in poor mechanical properties. The organic-inorganic composite porous antibacterial scaffold of Comparative Example 2 does not contain transition metal carbide nanosheets or nano-hydroxyapatite, thus failing to provide a framework structure for the Co hollow spheres loaded with carbon nanotubes, resulting in poor mechanical properties. The traditional Chinese medicine-based active bone growth-activating support implant material of Comparative Example 3 does not contain pharmacodynamic fillers, thus failing to adhere to the organic-inorganic composite porous antibacterial scaffold to enhance its stability, resulting in poor mechanical properties.

[0094] Experimental Example 2

[0095] Antibacterial test

[0096] Test samples: Traditional Chinese medicine active bone growth-activating support implant materials prepared in Examples 1-4 and Comparative Examples 1-3.

[0097] Test Method: Various types of bacteria can cause infections in implants. This experiment selected common Staphylococcus aureus and Escherichia coli as experimental bacteria for antibacterial testing. The test sample was designed as a flat cylinder with a diameter of 10 mm and a thickness of 2 mm. After UV sterilization, it was placed on a substrate coated with 10 mm of UV light. 6 Place the bacterial suspension of cfu / mL on agar medium, invert the petri dish, and incubate it in a constant temperature incubator at 37℃ for 24 hours. Then, observe the growth of the inhibition zone. The larger the diameter (mm) of the inhibition zone, the stronger the inhibitory effect on the experimental bacteria.

[0098] Figure 3The figures show the inhibition zone diameters of Examples 1-4 and Comparative Examples 1-3. As shown, the inhibition zone diameters for Staphylococcus aureus and Escherichia coli in Examples 1-4 were 39-45 mm and 35-43 mm, respectively, both ≥35 mm, indicating strong antibacterial activity. The inhibition zone diameters for Staphylococcus aureus and Escherichia coli in Comparative Examples 1-3 were 8-20 mm and 6-18 mm, respectively, both ≤20 mm, indicating moderate antibacterial activity. The organic-inorganic composite porous antibacterial scaffold in Comparative Example 1 did not contain Co hollow spheres loaded with carbon nanotubes, reducing the density of the scaffold's porous structure and weakening its antibacterial activity. The adsorption by bacteria reduces the loading capacity of the drug-efficacy filler and prevents the cobalt element from adhering to bacteria, resulting in mediocre antibacterial properties. The organic-inorganic composite porous antibacterial scaffold in Comparative Example 2 does not contain transition metal carbide nanosheets or nano-hydroxyapatite, which is not conducive to the loading of the drug-efficacy filler and also prevents the metal carbide nanosheets from exerting their antibacterial effect, resulting in mediocre antibacterial properties. The traditional Chinese medicine active bone growth-activating support implant material in Comparative Example 3 does not contain drug-efficacy fillers and cannot adhere to the organic-inorganic composite porous antibacterial scaffold, thus failing to work synergistically to enhance the antibacterial effect, resulting in mediocre antibacterial properties.

[0099] Experimental Example 3

[0100] Cartilage Repair Effect Experiment

[0101] Test samples: Traditional Chinese medicine active bone growth-activating support implant materials prepared in Examples 1-4 and Comparative Examples 1-3.

[0102] Test Method: Seventy New Zealand white rabbits, aged 3 months and weighing 1.8-2.4 kg, were randomly divided into 7 groups of 70 rabbits each. They were anesthetized via intravenous injection of 2.5% sodium pentobarbital in the ear. After proper anesthesia, the limbs were securely immobilized. The lateral edge of the patellar ligament was incised sequentially to fully expose the weight-bearing area of ​​the lateral femoral condyle at the distal end. A cylindrical defect with a diameter of 4 mm and a depth of 3 mm was created on this defect. The subchondral bone was drilled through, and blood clots within the defect were removed. Test samples were then inserted to fill the defect. The wound was sutured layer by layer. Postoperatively, the wound was disinfected with povidone-iodine, bandaged with gauze, and no external fixation was performed. Penicillin and streptomycin were administered intramuscularly for double antibiotic protection to prevent infection. The rabbits were individually housed postoperatively. CT scans were performed at 16 weeks to observe the cartilage repair. The International Cartilage Repair Society (ICRS) scoring criteria were used to score the repair and calculate the average value. The specific scoring criteria for the degree of defect repair and overall repair are shown below:

[0103] The scoring criteria for the degree of defect repair are as follows:

[0104] Same as the surrounding normal cartilage, 4 points;

[0105] Repairing 75% of the defect depth, 3 points;

[0106] Repairing 50% of the defect depth, 2 points;

[0107] Repairing 25% of the defect depth, 1 point;

[0108] No repairs, 0 points;

[0109] The scoring criteria for boundary integration are as follows:

[0110] No clear boundaries, completely integrated with the surrounding cartilage, 4 points;

[0111] Boundary <1mm, 3 points;

[0112] 75% integration, 25% with significant gaps >1mm, 2 points;

[0113] 50% integration, 50% with significant gaps >1mm, 1 point;

[0114] Integration level less than 25%, 0 points;

[0115] The scoring criteria for general appearance observation are as follows:

[0116] Smooth and intact surface, 4 points;

[0117] The surface is fibrous, 3 points;

[0118] Small cracks or scars are visible on the surface, 2 points;

[0119] A few large cracks are visible on the surface, 1 point;

[0120] No repair or complete deterioration, 0 points;

[0121] The overall restoration scoring criteria are as follows:

[0122] Grade I, completely normal, 12 points;

[0123] Grade II, well repaired, 8-11 points;

[0124] Level III, repairs have been made, but the results are unsatisfactory, 4-7 points;

[0125] Grade IV, no repair effect, 0-3 points.

[0126] Figure 4Figures show the cartilage repair results of Examples 1-4 and Comparative Examples 1-3. As shown, the defect repair degree and overall repair scores for Examples 1-4 were 3.4-3.9 and 10.3-11.8, respectively, indicating effective promotion of chondrocyte regeneration and good repair effect. The defect repair degree and overall repair scores for Comparative Examples 1-3 were 1.6-2.8 and 5.3-7.0, respectively, indicating that they could not effectively promote chondrocyte regeneration and the repair effect was average. The organic-inorganic composite porous antibacterial scaffold in Comparative Example 1 did not contain Co hollow spheres loaded with carbon nanotubes, which is not conducive to enhancing cell adhesion and signal transduction capabilities, and also limits the effectiveness of the drug-efficacy filler. The organic-inorganic composite porous antibacterial scaffold in Comparative Example 2 lacks transition metal carbide nanosheets and nano-hydroxyapatite, which reduces the density and continuity of the network structure, decreases the contact area with surrounding tissues, weakens signal transduction, and hinders the full exertion of the drug-efficacy filler, resulting in an ineffective promotion of chondrocyte regeneration and a mediocre repair effect. Similarly, the traditional Chinese medicine-based bone growth-activating support implant material in Comparative Example 3 lacks drug-efficacy fillers, preventing deep stimulation of chondrocytes through the dual action of the scaffold and filler, thus failing to effectively promote chondrocyte regeneration and resulting in a mediocre repair effect.

[0127] The above experimental results show that the mechanical properties, antibacterial properties, and cartilage repair effects of Examples 1-4 of the present invention are significantly better than those of Comparative Examples 1-3. Among them, Example 1, which uses an organic-inorganic composite porous antibacterial scaffold and a pharmacological filler, has better mechanical properties, stronger antibacterial properties, and better cartilage repair effects. By cross-linking and compositing Co hollow spheres loaded with carbon nanotubes with sodium alginate, nano-hydroxyapatite, and transition metal carbide nanosheets, an organic-inorganic composite porous antibacterial scaffold is formed. It has good mechanical properties and antibacterial properties, and can also stably support more pharmacological fillers and release them slowly. At the same time, the pharmacological fillers also further improve the stability of the scaffold structure. The synergistic effect of the two significantly enhances the antibacterial and osteogenic effects of the implanted material, achieving excellent bone repair effects.

[0128] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention.

[0129] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A bone growth-activating support implant material based on traditional Chinese medicine, characterized in that: The herbal active bone growth-activating support implant material comprises the following components in parts by weight: 10-20 parts of organic-inorganic composite porous antibacterial scaffold and 20-30 parts of medicinal filler; the organic-inorganic composite porous antibacterial scaffold comprises the following components in parts by weight: 10-15 parts of sodium alginate, 10-20 parts of transition metal carbide nanosheets, 5-8 parts of nano-hydroxyapatite, 20-30 parts of Co hollow spheres loaded with carbon nanotubes, and 6-8 parts of glucono-delta-lactone; the medicinal filler comprises the following components in parts by weight: 3-5 parts of Epimedium, 3-5 parts of Dioscorea opposita, 3-5 parts of Drynaria fortunei, 3-5 parts of Astragalus membranaceus, 3-5 parts of deer antler glue, 3-5 parts of frankincense, 3-5 parts of Cuscuta chinensis, 3-5 parts of myrrh, 3-5 parts of Lycium barbarum, 3-5 parts of Achyranthes bidentata, 3-5 parts of Ligustrum lucidum, 3-5 parts of oyster shell, and 3-5 parts of Rehmannia glutinosa. The preparation method of the organic-inorganic composite porous antibacterial scaffold specifically includes the following steps: (1) Add 2.0-3.0g of lithium fluoride to 40mL of 30% hydrochloric acid solution, stir at 50-60rpm and slowly add 1.0-2.0g of titanium aluminum carbide. After the addition is complete, stir at 30-40℃ for 24-36h. Centrifuge the mixture at 2000-4000rpm for 5-10min to remove the upper liquid. Wash the precipitate with 10% dilute hydrochloric acid 3-5 times, and then repeatedly centrifuge and wash with deionized water until the pH is 6.

0. Add the washed precipitate to 100mL of deionized water and sonicate in an ice bath for 0.5-1h. Centrifuge the obtained colloidal solution at 4000-5000rpm for 10-20min. Take the upper colloidal solution and filter it into a thin film using a vacuum circulating water filter. Dry it to obtain transition metal carbide nanosheets. (2) Dissolve 19.8g sodium gluconate in 300mL of deionized water, then add cobalt nitrate hexahydrate, stir evenly, turn on the preheating furnace, raise the temperature to 700-800℃ at a rate of 10℃ / min, then transfer the solution to the ultrasonic atomizer, turn on the ultrasonic device and pass nitrogen gas at 1.5L / min. The nitrogen gas can blow the product into the collection bottle filled with ethanol, collect the black solid, filter and wash with deionized water 3-5 times, and vacuum dry to obtain Co hollow spheres; (3) Place the Co hollow spheres described in step (2) in a tube furnace, raise the temperature to 700°C at a rate of 8-10°C / min under an argon atmosphere of 80 mL / min, then introduce a mixture of acetylene and hydrogen at a rate of 80 mL / min, keep warm for 20-40 min, stop introducing acetylene and hydrogen, and cool to room temperature under argon protection to obtain Co hollow spheres loaded with carbon nanotubes. (4) Disperse the transition metal carbide nanosheets and nano hydroxyapatite described in step (1) in 50 mL of deionized water, sonicate for 1-2 h, centrifuge, freeze-dry the precipitate, mix it evenly with the Co hollow spheres loaded with carbon nanotubes described in step (3), and then anneal it in a nitrogen atmosphere at 350-400 °C for 1-2 h to obtain the composite material. (5) Disperse the composite material described in step (4) in 50 mL of deionized water, sonicate for 1-2 h, add 1.0-1.5 g of sodium alginate, stir magnetically for 20-30 min, and use it as the liquid to be used. Weigh 0.2-0.3 g of calcium carbonate and add it to 5 mL of deionized water, sonicate for 20-30 min, and then add the calcium carbonate suspension to the liquid to be used at a speed of 1000-2000 rpm. After dispersing evenly, add gluconolactone, stir evenly, transfer to a 24-well plate, react at 4 °C for 12-24 h, and then freeze-dry at -80 °C for 36-48 h to obtain an organic-inorganic composite porous antibacterial scaffold.

2. A method for preparing a bone growth-activating support implant material based on traditional Chinese medicine according to claim 1, characterized in that: Specifically, the following steps are included: S1. Place Epimedium, Dioscorea opposita, Drynaria fortunei, Astragalus membranaceus, deer antler glue, frankincense, Cuscuta chinensis, myrrh, Lycium barbarum, Achyranthes bidentata, Ligustrum lucidum, oyster shell, and Rehmannia glutinosa in a decoction machine with 10-15 times the amount of water and soak for 2-3 hours. Decoction 1-2 times, extract by gentle boiling for 2-3 hours. Combine the decoctions, freeze-dry the residue for later use. Concentrate the collected filtrate to 1 / 6 to 1 / 5 of the original volume under vacuum pressure of -0.06 MPa and temperature of 40-50℃. Then pour the freeze-dried residue powder into the concentrated liquid, sonicate for 30-40 minutes, and magnetically stir for 1-2 hours to obtain the medicinal filler. S2. Immerse the organic-inorganic composite porous antibacterial scaffold in the medicated filler material described in step S1 for 2-3 hours. Remove it and perform pretreatment. Then, use a dropper to add the remaining medicated filler material drop by drop, allowing it to stand for 30-50 seconds after each addition. After the addition is complete, freeze-dry it in a vacuum at -80℃ for 24-36 hours. Then, place it in a clean bench and irradiate it with ultraviolet light for 8 hours to sterilize it, thus obtaining the Chinese medicine active bone growth activating support implant material.

3. The preparation method of the bone growth-activating support implant material based on traditional Chinese medicine according to claim 2, characterized in that: In step S2, during the pretreatment process, the sample is frozen in a -20°C freezer for 3-4 hours.

4. The preparation method of the bone growth-activating support implant material of traditional Chinese medicine according to claim 3, characterized in that: In step (2), the amount of cobalt nitrate hexahydrate added is 24.2-26.2g.

5. The preparation method of the bone growth-activating support implant material according to claim 4, characterized in that: In step (5), the amount of gluconolactone added is 0.6-0.8g.

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