WO2011057521A1 - Matériau composite magnétique et son application dans la régénération et la réparation du tissu osseux - Google Patents

Matériau composite magnétique et son application dans la régénération et la réparation du tissu osseux Download PDF

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WO2011057521A1
WO2011057521A1 PCT/CN2010/077114 CN2010077114W WO2011057521A1 WO 2011057521 A1 WO2011057521 A1 WO 2011057521A1 CN 2010077114 W CN2010077114 W CN 2010077114W WO 2011057521 A1 WO2011057521 A1 WO 2011057521A1
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nanoparticles
magnetic
bone
nha
organic solvent
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English (en)
Chinese (zh)
Inventor
许海燕
孔桦
齐晓谨
孟洁
顾宁
张宇
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Institute of Basic Medical Sciences of AMMS
Institute of Basic Medical Sciences of CAMS and PUMC
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Institute of Basic Medical Sciences of AMMS
Institute of Basic Medical Sciences of CAMS and PUMC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention relates to a magnetic composite material for bone tissue regeneration and repair and a method of preparing the same.
  • the invention also relates to an article made from the magnetic composite and to the use thereof. Background technique
  • Bone injury and bone defects are clinically common diseases, often requiring bone grafting [1].
  • Traditional medicine relies on autologous bone [2] and allogeneic bone [3-4] for bone repair for bone defects caused by injury or disease.
  • Autologous bone grafting has a good repair effect, but it has limited supply and requires secondary surgery, and the postoperative complications can reach 8%.
  • Allogeneic bone has shortcomings such as immunogenicity and pathogenicity, so it is not an ideal bone repair material.
  • Bone tissue engineering that emerged in the 1980s changed the traditional treatment model for repairing trauma at the expense of autologous tissue damage.
  • a small amount of tissue cells can be repaired and expanded in vitro to repair bone defects.
  • it can be shaped to achieve perfect morphological repair, which opens up a new way for the ultimate realization of non-invasive repair wound and true functional reconstruction. .
  • hydroxyapatite especially hydroxyapatite nanoparticles (nHA), as a bioceramic material
  • HA hydroxyapatite
  • nHA hydroxyapatite nanoparticles
  • Ca 2+ in the ruthenium molecule can exchange with a carboxyl group-containing amino acid, protein, organic acid, etc., has good bone conduction properties and biological activity, can form a strong bone bond with bone tissue, promote bone growth, and phase It is relatively stable, non-toxic and inflammatory, and is recognized as a good substitute for bone repair.
  • HA also has its own shortcomings, such as low compressive strength, poor fatigue resistance, poor bioabsorbability, slow replacement speed, and looseness, migration, and destruction after implantation in the body.
  • nHA hydroxyapatite nanoparticles
  • the grain size and grain boundary width of hydroxyapatite nanoparticles (nHA) are limited to nanometers. The level of magnitude.
  • the surface area per unit mass of nano-sized particles is significantly larger than that of micro-sized particles, so that the number of atoms at the surface of the particles is significantly increased, and the activity of the particles is improved. Therefore, nHA particles are more conducive to integration with bone tissue than micron-sized HA, and bone conduction, solubility, and mechanical properties are also improved compared to micron-sized HA.
  • nHA exhibits certain specificities in function, such as inhibition of the growth of some tumor cells, but has no negative effects on normal cells [22]. Therefore, nHA is more widely used in the field of bone tissue engineering.
  • hydroxyapatite As a bone tissue engineering material, single-component hydroxyapatite has the disadvantages of low strength, poor toughness, and difficulty in bearing large loads or impacts, which limits its use as an implant material. In order to improve the mechanical properties of hydroxyapatite ceramic materials, it has been clinically popularized. Many laboratories at home and abroad have used hydroxyapatite in combination with other materials to improve their performance.
  • the matrix materials currently used mainly include biodegradable natural biomaterials (eg collagen [5-8], hyaluronic acid, chitosan, silk fibroin, etc.) and synthetic polymeric materials (eg polylactic acid (PDLLA)). , polyglycolic acid, lactic acid-glycolic acid copolymer (PLGA), etc.).
  • Collagen has a good affinity for Ca 2+ in solution and acts as a nucleation and mineralization template during HA crystallization.
  • Du[5], Liu[6], K.Rezwan[7] and other nano-hydroxyapatite/collagen composites were observed by X-ray diffraction, scanning electron microscopy and transmission electron microscopy. Nano-hydroxyapatite and type I collagen were found. The self-assembled structure of the molecule is similar to the microstructure of the natural bone.
  • Venugopal J [8] found that electrospun scaffolds of collagen/hydroxyapatite can support cell proliferation. Compared with collagen scaffolds alone, electrospinning of collagen/hydroxyapatite can significantly increase osteoblast mineralization.
  • Chitosan (CS) is a natural biodegradable polysaccharide with excellent properties such as non-toxic, non-irritating, biocompatible, biodegradable, and easy to modify, but lacks bone bonding biological activity, lacking Elasticity and flexibility.
  • the combination of hydroxyapatite and chitosan combines the advantages of both, overcoming the shortcomings of the two single-component materials.
  • Chesnutt BM [9] found that the adhesion and proliferation of cells on hydroxyapatite/chitosan scaffolds were increased.
  • Silk fibroin is a natural high-molecular fibrin extracted from silk and has many excellent properties such as good biocompatibility and mechanical properties; good biodegradability; support for cell adhesion, proliferation and differentiation. Wait.
  • Silk fibroin contains more hydroxyl and carboxyl groups, which can bind tightly with calcium ions and induce hydroxyapatite to mineralize and crystallize on silk proteins. Assembly of nanocomposite materials.
  • [10-12] silk fibroin as a template provides an active site for nucleation and crystal growth of hydroxyapatite crystals, promotes crystal growth of hydroxyapatite, and affects hydroxyapatite crystals. Self-assembly preferred orientation along the c-axis.
  • hydroxyapatite material makes it difficult for hydroxyapatite particles to migrate to surrounding tissues, which overcomes the disadvantages of looseness, migration and damage that may occur after hydroxyapatite materials are implanted into the body. Moreover, the bioabsorbability of the hydroxyapatite can be improved, and at the same time, the effect of not damaging the surrounding soft tissue can be achieved.
  • nHA I PDLLA composites Deng [13] and other synthetic nHA I PDLLA composites, the mechanical properties of the material test results show that within a certain range, with the increase of nHA content, the tensile strength of the composite material is improved, it is assumed that this is due to the shortness of nHA
  • the fiber is filled into the organic matrix to increase the strength of the polymer.
  • Nie H [14] et al. used HA/PLGA scaffolds as carriers to carry DNA/chitosan particles to promote cell adhesion and gene transfection, thereby promoting bone regeneration.
  • Recently, others have [15] co-combined hydroxyapatite, collagen, chitosan, and PDLLA to prepare cell scaffolds for carrying bone-forming proteins to promote bone regeneration.
  • the artificial bone fillers used in the clinical treatment of bone defects mainly include: calcium phosphate cement [16], calcium sulfate [17], coral hydroxyapatite [18] and so on.
  • calcium sulfate and calcium phosphate are widely used in clinical practice.
  • calcium sulfate bone powder is stronger than calcium phosphate after solidification, has a strong supporting effect, and has a faster degradation rate than calcium phosphate.
  • some composite materials are used clinically for the filling of bone defects, such as mixed filling of autologous bone, artificial bone and periosteum fragments [19], including nano-hydroxyapatite/polyamide 66 composite bone filling material [20] and nanometer. Hydroxyapatite/collagen artificial bone [21] and the like.
  • a magnetic composite material for bone tissue regeneration and repair consists of the following components:
  • nHA hydroxyapatite nanoparticles
  • organic solvent is selected from the group consisting of tetrahydrofuran (THF), dimethylformamide (DMF), dimethylacetamide (DMAc), Chloroform or dioxane.
  • the present invention also provides a method of preparing the magnetic composite material, which comprises dispersing components a), b) and c) mechanically in an organic solvent to make Y-Fe 2 0 3 nanoparticles and hydroxyphosphorus
  • the gray stone nanoparticles are evenly distributed in the continuous phase of the polymer material to form a uniform composite material.
  • the invention also provides an article made from the magnetic composite.
  • each particle When the size of the magnetic nanoparticles is small to a certain critical size, each particle is a single magnetic domain. At this time, the thermal kinetic energy of the electrons in the particle exceeds the electron spin orientation energy, and the magnetic moment is randomly arranged, and the magnetic nanoparticles are arranged. From ferromagnetic or ferrimagnetic to superparamagnetic. The critical dimensions of different magnetic materials entering superparamagnetic are different. For Y-Fe 2 0 3 and Fe 3 0 4 nanoparticles, the critical dimensions are 14 nm and 20 nm, respectively.
  • magnetic nanoparticles are mainly manifested in superparamagnetism and magnetic susceptibility. Due to the special magnetic properties of magnetic nanoparticles, these particles are in magnetic recording materials, magnetic liquids, biomedicine, sensors, catalysis, permanent magnet materials, pigments, Radar wave absorbing materials and other fields have broad application prospects.
  • Figure 1 is a magnetization curve of a Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film.
  • 2 is a transmission electron micrograph of Y-Fe 2 0 3 nanoparticles having DMSA attached to the surface.
  • Figure 3 is a SEM picture of a Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film.
  • FIG. 4 is a graph showing the pH change of a phosphate buffer solution of a non-woven film of Y- Fe 2 0 3 /nHA/PDLLA magnetic nanofibers.
  • Figure 5 is a graph showing the proliferation of MC3T3-E1 on a nHA/PDLLA nanofiber nonwoven film and a Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film in a minimal medium, wherein (A) indicates Increased on nHA/PDLLA nanofiber nonwoven film without applying magnetic field (B) indicates the proliferation on the nHA/PDLLA nanofiber nonwoven film under the application of a magnetic field; (C) indicates the Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber without applying a magnetic field. Proliferation on the nonwoven film; (D) shows the proliferation on the Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film under application of a magnetic field.
  • Figure 6 is a graph showing the proliferation of MC3T3-E1 on the nHA/ PDLLA nanofiber nonwoven film and the Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film in the induction medium, wherein (A) indicates Proliferation on nHA/PDLLA nanofiber nonwoven film without applying magnetic field; (B) showing proliferation on nHA/PDLLA nanofiber nonwoven film under applied magnetic field; (C) indicating no magnetic field applied Next, the proliferation on the Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film; (D) indicates the Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film under the applied magnetic field The proliferation on the situation.
  • Figure 9 is a SEM image of the morphology and secretion of bone matrix of pre-osteoblasts cultured on nHA/PDLLA nanofibers for 21 days.
  • Figure 10 is a three-dimensional reconstruction of the CT scan of the rabbit bone defect after 40 and 70 days of bone grafting.
  • a and b are images of autologous bone grafts 40 and 70 days later;
  • c and d are images of magnetic nanofiber composite bone grafts 40 and 70 days later.
  • the present invention provides a magnetic composite for bone tissue regeneration and repair, consisting of the following components:
  • hydroxyapatite nanoparticles nHA
  • organic solvent selected from the group consisting of tetrahydrofuran (THF), dimethylformamide (DMF), dimethylacetamide (DMAc), Chloroform or dioxane
  • THF tetrahydrofuran
  • DMF dimethylformamide
  • DMAc dimethylacetamide
  • Chloroform or dioxane the hydroxyapatite nanoparticles have a particle diameter of 30 to 50 nm
  • the y-Fe 2 0 3 nanoparticles have a particle diameter of 14 nm.
  • the y-Fe 2 0 3 nanoparticles are preferably surface 203 is connected to the nanoparticles dimercaptosuccinic acid (DMSA) in the Y -Fe.
  • DMSA dimercaptosuccinic acid
  • the polymeric material is preferably polylactic acid.
  • the article is a nanofiber nonwoven film, a nonwoven felt, a foam, a smooth film, a sheet, a tube or a surface coating, or other geometric shaped article.
  • the nanofiber nonwoven film has a thickness of about 20 microns.
  • the composite is prepared as follows:
  • Y-Fe 2 0 3 nanoparticles were dispersed in 100 ml of an organic solvent.
  • Ultrasonic vibration dispersion method is used, ultrasonic in the ultrasonic bath for 0.5 ⁇ 15min (ultrasonic power: 10 ⁇ 80%), and then ultrasonically probed for 1 ⁇ 10 times, each time 1 ⁇ 120 seconds.
  • the organic solvent is selected from the group consisting of tetrahydrofuran (THF), dimethylformamide (DMF), dimethylacetamide (DMAc), chloroform or dioxane.
  • the present invention provides a magnetic nanofiber nonwoven film material prepared by electrospinning using the above composite material.
  • the above composite material is added to a syringe pump, and the spinning solution is sprayed from the head at room temperature under the action of pumping or gravity.
  • a high voltage electric field of 15 kV is applied between the syringe pump nozzle and the receiving plate. Due to the repulsion of the surface charge of the polymer solution, the droplets are stretched into a Taylor cone shape, stretched into fibers under the action of an electric field, and the receiving plate is rotated to collect the fibers at a speed of between 100 and 600 nm, according to the receiving plate. The speed of the directional or non-oriented magnetic nanofiber nonwoven film is obtained.
  • the receiving plate When the fibers are required to be randomly arranged, the receiving plate is at a speed of 0-10 rpm. Rotation; When the fiber orientation is required, the receiving plate rotates at a speed of 100 rpm.
  • the present invention provides a nonwoven felt.
  • the multilayer electrospun film was treated by a random needle method to obtain a nonwoven felt material.
  • the present invention provides a foaming material.
  • a foaming agent is added per 100 ml of the organic solvent, and the resulting solution is cast into a mold of a designed shape to obtain a foaming material.
  • the present invention provides a cast film.
  • the composite material is cast into a mold of a designed shape to obtain a cast sheet.
  • the sheet thickness can be controlled by the volume of the solution being cast.
  • the present invention provides a cast tube.
  • the tubular mold is dipped and dried in the composite material and repeated several times until the desired thickness is reached.
  • the mold is taken out to obtain a cast pipe.
  • the present invention provides an extruded tube or membrane.
  • the composite material is added to the aqueous medium to coprecipitate the components in the solution, and after the precipitate is dried, it is extruded by an extruder die to obtain a sheet or a tube.
  • the present invention provides an in vitro cell culture plate comprising the above-described magnetic nanofiber nonwoven film and a base material, wherein a magnetic nanofiber nonwoven film is sprayed on the base material to form a film surface layer, Then, the substrate material having the film surface layer is used as a base to be processed into an in vitro cell culture plate.
  • the base material may be a polyurethane sheet, a polystyrene sheet, a silicone rubber sheet, or a glass having a polymer coating.
  • the present invention provides a use for in vitro bone tissue culture, wherein pre-osteoblasts, or osteoblasts are grown on magnetic nanofiber nonwoven hair
  • the felt or the foam material is placed in a bioreactor and subjected to in vitro dynamic culture under the application of an applied magnetic field.
  • Hydroxyapatite nanoparticles are commercially available.
  • the polymer material used in the present invention is commercially available and has a number average molecular weight of 50,000 to 200,000.
  • FeCl 3 (0.1 M) and FeS0 4 (0.06 M) aqueous solution were prepared under nitrogen, and 200 mL of ammonia water UM) was added dropwise to the aqueous solution at room temperature with vigorous stirring. After thirty minutes, the obtained Fe 3 0 4 nanoparticles were collected with a magnetic field and washed three times with water. These particles are re-dispersed in water, and the ventilation oxidation of Y-Fe 2 0 3 at 95 ° C in air.
  • y-Fe 2 0 3 nanoparticles y-Fe 2 0 3 /DMSA
  • DMSA transmission electron microscopy
  • PLLA a stainless steel anchor stirrer controlled by a rotary motor (50 rpm) to form a Y-Fe 2 0 3 /nHA/PDLLA/DMAc composite solution with good fluidity and uniform mixing.
  • PLLA a stainless steel anchor stirrer controlled by a rotary motor (50 rpm) to form a Y-Fe 2 0 3 /nHA/PDLLA/DMAc composite solution with good fluidity and uniform mixing.
  • the nozzle is a 9# syringe needle, the nozzle is connected to the positive pole of the high-voltage electrostatic generator, and the receiving tray is connected to the cathode.
  • the distance between the receiving tray and the nozzle is 25cm, between the nozzle of the syringe pump and the receiving plate.
  • the receiving tray is slowly rotated to uniformly receive the spun fiber, and a Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film having a fiber diameter of 100 to 600 nm is obtained.
  • Example 1 In a small beaker of 25 ml, 20 ml of trichloromethane (CHC1 3 ) was added, and 0.5 g of the dried Y-Fe 2 0 3 nanoparticles prepared in Example 1 was dispersed in trichloromethane, and uniformly dispersed by ultrasonic waves. , obtaining a solution of Y-Fe 2 0 3 nanoparticles;
  • the nozzle is a 9# syringe needle.
  • the nozzle is connected to the positive electrode of the high voltage electrostatic generator.
  • the receiving tray is connected to the cathode. The distance between the receiving tray and the nozzle is 25cm.
  • the nozzle and receiving plate of the injection pump are used. Electro-spinning was carried out by applying a voltage of 15 kV; the receiving disk was slowly rotated to uniformly receive the spun fiber, and a y-Fe 2 0 3 /nHA/PHBV magnetic nanofiber nonwoven film having a fiber diameter of 100 to 600 nm was obtained.
  • Example 7 Add 0.5g of foaming agent benzoyl peroxide (BPO) to the solution of the above step C and mix it evenly. Cast the solution into a cylindrical glass mold with a diameter of 35mm. After the solvent is evaporated, remove the mold. The mixture was dried in a vacuum oven at 50 ° C for 72 hours to thoroughly remove the residual solvent to obtain a magnetic foam composite.
  • BPO benzoyl peroxide
  • Example 1 In a small beaker of 25 ml, 20 ml of trichloromethane (CHC1 3 ) was added, and 0.5 g of the dried Y-Fe 2 0 3 nanoparticles prepared in Example 1 was dispersed in trichloromethane, and uniformly dispersed by ultrasonic waves. , obtaining a solution of Y-Fe 2 0 3 nanoparticles;
  • the above composite material was cast into a circular glass mold having a diameter of 8 cm. After the solvent was evaporated, the mold was removed, and dried in a vacuum oven at 50 ° C for 72 hours to completely remove the residual solvent to obtain a magnetic sheet.
  • the tubular mold is repeatedly dip coated in the above composite material. After the solvent is evaporated, the mold is removed, and dried in a vacuum oven at 50 ° C for 72 hours to completely remove the residual solvent to obtain a magnetic tube.
  • PCL polycaprolactone
  • the above composite material is added to the aqueous medium to coprecipitate the components in the solution, and the precipitate is dried and then granulated, and the granules are extruded through an extruder die to obtain a sheet.
  • the above composite material is added to the aqueous medium to coprecipitate the components in the solution, and the precipitate is dried and then granulated, and the granules are extruded through an extruder die to obtain a sheet.
  • PCL polycaprolactone
  • the above composite material is added to an aqueous medium to coprecipitate the components in the solution, and after the precipitate is dried, it is extruded by an extruder die to obtain a sheet.
  • Example 12 A In a small beaker of 25 ml, 20 ml of dioxane was added, and 0.5 g of the dried Y-Fe 2 0 3 nanoparticles prepared in Example 1 was dispersed in dioxane, and uniformly dispersed by ultrasonic wave to obtain Y- a solution of Fe 2 0 3 nanoparticles;
  • the tubular mold is repeatedly dip coated in the magnetic composite material. After the solvent is evaporated, the mold is removed, and dried in a vacuum oven at 50 ° C for 72 hours to completely remove the residual solvent to obtain a magnetic tube.
  • control material is a non-magnetic film of nHA/PDLLA nanofibers without a magnetic material, and the preparation method is as follows:
  • DMAc dimethylacetamide
  • the nozzle is a 9# syringe needle.
  • the nozzle is connected to the positive pole of the high voltage electrostatic generator.
  • the receiving tray is connected to the cathode. The distance between the receiving tray and the nozzle is 25cm.
  • the nozzle and receiving plate of the injection pump are used. Electrostatic spinning was carried out by applying a voltage of 15 kV; the receiving disk was slowly rotated to uniformly receive the spun fiber, and after the spinning solution was completely sprayed, a nHA/PDLLA nanofiber nonwoven film having a fiber diameter of 100 to 600 nm was obtained.
  • PLLA polylactic acid
  • the Y-Fe 2 0 3 /nHA/PDLLA magnetic nanofiber nonwoven film prepared in Example 2 was used as an example to characterize the performance:
  • the nanofiber nonwoven film prepared has paramagnetic properties due to the addition of superparamagnetic Y-Fe 2 0 3 nanoparticles.
  • the magnetization reaches a saturation value of 0.0492 emu. /g, becomes a magnetic nanofiber nonwoven film.
  • the magnetic nanofiber nonwoven film is light brownish yellow.
  • the color is derived from superparamagnetic Y-Fe 2 0 3 nanoparticles, and the fiber membrane is soft and about 20 microns thick.
  • Fig. 3 it can be seen from the scanning electron microscope that most of the magnetic nanofibers have a diameter in the range of 100 to 600 nm and overlap each other to form a three-dimensional network structure similar to a natural extracellular matrix; the surface of the spun fiber is rough, The prominent particulate matter is nHA nanoparticles. Degradation performance of magnetic nanofiber nonwoven film
  • the magnetic nanofiber nonwoven membrane was immersed in the phosphate buffer solution, and the pH change of the phosphate buffer environment was observed within two months.
  • the results are shown in Fig. 4, wherein the control (PBS) means a bottle.
  • the blank PBS buffer without soaking the sample was placed under the same conditions (37 ° C), and its pH slightly decreased due to a small amount of carbon dioxide dissolved in the air during the 50-day experiment.
  • the pH drop of the PBS buffer in which the composite was soaked was mainly due to degradation of the material.
  • lactic acid produced by the degradation of PDLLA leads to an increase in environmental acidity, due to the addition of nHA to the composite. Partial acidity was neutralized, so the pH of the soak was reduced from the initial 7.4 to 5.5 during the two-month test period.
  • Table 1 Surface chemical composition of the three materials obtained by XPS.
  • the magnetic nanofiber nonwoven membrane has the function of promoting pro-osteogenic proliferation, differentiation into bone and mineralization.
  • Figures 5 and 6 show the mouse pre-osteoblast MC3T3-E1 in nHA/PDLLA nanofiber nonwoven film (A, B) and y-Fe 2 0 3 /nHA/ with and without magnetic field application. Proliferation on PDLLA magnetic nanofiber nonwoven film (C, D). Table 2 and Table 3 show the significant difference analysis of cell proliferation of each group of materials under the conditions of basic medium and induction medium, respectively. As can be seen from Figures 5 and 6, the number of cells growing on the magnetic nanofiber nonwoven membrane at various time points during the 13-day culture period in the basic/induction medium with or without an applied magnetic field. More than nHA/PDLLA nanofiber nonwoven film, and the number of cells growing under the application of external magnetic field is more than the case where no external magnetic field is applied.
  • the magnetic nanofiber nonwoven film in the case of combined application of a magnetic field, the number of cell proliferation is significantly greater than the number of cells on the control material (ie, 0.05 ⁇ 0.05).
  • the number of cells proliferating on the magnetic nanofiber nonwoven film is also significantly higher than that on the control material at 6-15 days. (PO.05). This indicates that the magnetic nanofiber nonwoven film itself can promote the proliferation of pre-osteoblasts.
  • the amount of cell proliferation on the non-woven membrane of magnetic nanofibers was always significantly higher than that of the control group (PO.05) within 13 days of culture, regardless of whether or not a magnetic field was applied.
  • the number of cells on the non-woven membrane of the magnetic nanofibers begins to decrease, indicating that some of the pre-osteoblasts have differentiated into bone cells.
  • the magnetic nanofiber nonwoven film itself can also promote the proliferation of pre-osteoblasts and differentiation into osteoblasts.
  • we can also find that the combined application of external magnetic field can enhance the promotion of cell proliferation by magnetic nanofiber nonwoven membrane.
  • the bone matrix, the pre-osteoblasts on the magnetic nanofiber nonwoven membrane have mostly differentiated into osteoblasts, forming mineralized knots, and secreting a large number of matrices (as shown in Figures 8a and 8b).
  • the cells grown on the control material partially differentiated into osteoblasts, and mineralized junctions appeared, but the secretory matrix was few (as shown in Figure 9).
  • Healthy adult New Zealand white rabbits were selected and divided into two groups according to the random method: one group was the autologous bone control group, and the other group was the magnetic nanofiber non-woven membrane group, and the bone defect was made.
  • the bone and magnetic nanofibers were taken at the tibia.
  • the non-woven membrane material is filled to the bone defect, and the skin is conventionally sutured.
  • All experimental animals were intramuscularly injected with anti-adhesive for 3 days, and they were housed in rabbit cages and freely active. A uniform static magnetic field was applied around the rabbit cage of the female material group. CT scans were performed on rabbits 40 and 70 days after surgery.
  • the new bone volume at the bone graft site of the magnetic nanofiber nonwoven membrane material is almost equal to the bone volume at the autologous bone graft site (as shown in Figures 10a and 10b).
  • the volume of new bone at the bone graft site of both materials increased significantly compared with 40 days after surgery. More notably, the new bone at the bone graft site of the magnetic material is even larger than the autologous bone graft (as shown in Figures 10c and 10d). This indicates that the magnetic nanofiber nonwoven film material has a good in vivo induced osteogenesis under magnetic field conditions.

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Abstract

La présente invention a pour objet un matériau composite magnétique constitué : a) de 10 à 50 grammes d'un polymère pour 100 mL de solvant organique, ledit polymère étant choisi dans le groupe comprenant l'acide polylactique, l'acide polyglycolique, un copolymère acide lactique - acide glycolique, la polycaprolactone, le polyamide et l'acide polyhydroxybutyrique; b) de 10 grammes de nanoparticules d'hydroxyapatite pour 100 mL de solvant organique; et c) de 2,5 grammes de nanoparticules de γ-Fe2O3 pour 100 mL de solvant organique, ledit solvant organique étant choisi dans le groupe comprenant le tétrahydrofuranne (THF), le diméthylformamide (DMF), le diméthylacétamide (DMAc), le chloroforme et le dioxane. La présente invention concerne également l'application du matériau composite magnétique dans la régénération et la réparation du tissu osseux, le procédé pour préparer le matériau composite magnétique et le produit fabriqué à partir dudit matériau composite magnétique.
PCT/CN2010/077114 2009-11-10 2010-09-19 Matériau composite magnétique et son application dans la régénération et la réparation du tissu osseux Ceased WO2011057521A1 (fr)

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CN 200910211585 CN102049066B (zh) 2009-11-10 2009-11-10 一种磁性复合材料及其在骨组织再生和修复中的应用
CN200910211585.0 2009-11-10

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