CN111068122A - Biological composite material, preparation method thereof and biological scaffold - Google Patents

Biological composite material, preparation method thereof and biological scaffold Download PDF

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Publication number
CN111068122A
CN111068122A CN201811216198.1A CN201811216198A CN111068122A CN 111068122 A CN111068122 A CN 111068122A CN 201811216198 A CN201811216198 A CN 201811216198A CN 111068122 A CN111068122 A CN 111068122A
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biological
bone
lithium
biocomposite
composite material
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王新峦
秦岭
李玲
曹会娟
孟祥波
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • 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
    • 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
    • A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus

Abstract

The invention discloses a biological composite material, a preparation method thereof and a biological scaffold. The biological composite material comprises a biological compatible material and an effective dose of bone growth promoter, and the bone growth promoter is dispersed in the biological compatible material; wherein the bone growth promoter includes a lithium source providing lithium ions. The preparation method comprises the steps of mixing a lithium source for providing lithium ions, components contained in the biocompatible material and a solvent to prepare slurry, drying the slurry and the like. The biological scaffold comprises the biocomposite material. The biological composite material and the biological scaffold have excellent function of promoting the generation of the bone/cartilage, and have the advantages of high stability and safety of the function of promoting the generation of the bone/cartilage and low cost.

Description

Biological composite material, preparation method thereof and biological scaffold
Technical Field
The invention belongs to the field of biological materials, and particularly relates to a biological composite material, a preparation method thereof and a biological scaffold.
Background
Bone defects are a difficult point in the surgical treatment of bone. Factors that lead to bone defects include trauma, osteoporotic fractures, tumors, and bone necrosis. Autologous bone grafting in current methods of clinical treatment of bone defects increases the patient's chances of additional trauma and is limited in availability. Allogeneic bone grafts avoid the disadvantages of autologous bone, but have potential opportunities for infection and rejection. The method adopts a material compounded by a degradable carrier and a growth factor for repairing bone defects, which is a research hotspot at present, wherein the most commonly used Bone Morphogenetic Protein (BMP) is a growth differentiation factor and can be used for promoting the growth of local bones, but the protein is degraded quickly, and needs a large dose to keep the effect, so that the cost is high; the physical and chemical properties are unstable, and the activity of the carrier is difficult to maintain when the carrier is mixed with other carriers; the residence time in the defect area is short. Gene therapy is only in animal experiment stage because of its safety problem, and it can not be applied in clinic at present.
Endogenous growth factors (e.g., BMP, IGF-1, TGF- β, etc.) may be used to promote local bone growth, but such proteins degrade rapidly, require large doses to maintain their effectiveness, are expensive, are physically and chemically unstable, are difficult to maintain their activity when mixed with other carriers, are damaged, degraded or cleared by enzymes, or bind proteins to inhibit their activity, and are controversial in dosage and safety.
Other growth-promoting factors have been developed to promote local bone growth, such as a distributively degradable bioactive implant material containing growth-promoting factors, which is composed of a medical rapidly degradable polymer component containing growth-promoting factors and a medical slowly degradable polymer component containing biomimetic apatite component in a blending or copolymerization manner, wherein the growth-promoting factors include at least one of the growth-promoting factors icariin, astragalus polysaccharides, cartialgenous polypeptide, drynaria extract, woodlouse extract, and teasel root extract in the form of natural components or natural component extracts. In another disclosed bone repair material, it comprises a biodegradable polymer, a biodegradable inorganic substance, and a biodegradable metallic material. The biodegradable metal material has excellent biocompatibility and bone inducing activity, so that the biodegradable metal material has bone formation promoting effect. Although other somatomedins have a certain bone formation promoting effect, their sources are limited, and there are disadvantages in that the components such as extracts are not determined in terms of their components or their structures are unstable.
Therefore, the existing bioactive materials containing the growth factors have the problems of unsatisfactory bone growth, safety and the like due to unstable structure, uncertain components, uncertain safety and the like of the contained growth factors, so that the corresponding biological scaffold also has the problems of unsatisfactory bone growth, safety and the like.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a biological composite material and a preparation method thereof, so as to solve the technical problems of the existing biological active material containing growth factors that the growth of bones or cartilages is not ideal due to unstable structure, uncertain components, unsafe condition and the like of the contained growth factors.
The invention also aims to provide a biological scaffold to solve the technical problems of unsatisfactory bone or cartilage growth and safety of the existing biological scaffold.
In order to achieve the object, according to one aspect of the present invention, there is provided a biocomposite material. The biological composite material comprises a biological compatible material and an effective dose of bone growth promoter, and the bone growth promoter is dispersed in the biological compatible material; wherein the bone growth promoter includes a lithium source providing lithium ions.
In another aspect of the invention, a method for preparing a biocomposite material is provided. The preparation method comprises the following steps:
mixing a lithium source for providing lithium ions, components contained in a biocompatible material and a solvent to prepare slurry;
and drying the slurry.
In yet another aspect of the present invention, a biological stent is provided. The material of the biological scaffold comprises the biological composite material or the biological composite material prepared by the preparation method.
Compared with the prior art, the biological composite material adopts a lithium source providing lithium ions as a bone growth promoter, namely as an active factor for promoting bone growth and repair, on one hand, the biological composite material can effectively promote the growth and repair of local bone and cartilage, and endows the biological composite material with an excellent function of promoting bone/cartilage generation; on the other hand, the source of lithium is wide, the price is low, the structure and the physicochemical property are stable, and the toxicity or the side effect is small, so that the stability and the safety of the function of promoting the generation of the bone/cartilage of the biological composite material are effectively improved, and the cost is reduced.
The preparation method of the biological composite material provided by the invention mixes the lithium source for providing lithium ions with the components contained in the biological compatible material, and the lithium source has wide source, low price, stable structure and physicochemical property and high safety, so that the preparation method can effectively ensure the stability of the lithium source as an active factor for promoting the repair of bones and cartilages in the preparation process, thereby ensuring the function of stably promoting the generation of bones/cartilages of the prepared biological composite material, and endowing the prepared biological composite material with high safety and low production cost.
The biological scaffold of the invention has the function of stably and safely promoting the generation of bone/cartilage and has low cost because of containing the biological composite material of the invention.
Drawings
The invention will be further described with reference to the accompanying drawings and examples, in which:
FIG. 1 is a schematic process flow diagram of a method for preparing a biocomposite according to an embodiment of the present invention;
FIG. 2 is a diagram of a biological scaffold prepared from the biocomposite material of example 1 of the present invention;
fig. 3 is a micro-CT scanning photograph of a femur in a repair experiment of a bio-composite bone in example 1 and comparative example 1 of the present invention, wherein fig. 3-a is a micro-CT photograph of a control group, fig. 3-B is a micro-CT photograph of a blank stent group, and fig. 3-C is a micro-CT photograph of a lithium chloride stent group.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the embodiments and the accompanying drawings. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The mass of each component mentioned in the description of the embodiment of the present invention may not only refer to the specific content of each component, but also represent the proportional relationship of the mass between each component, and therefore, it is within the scope of the disclosure of the description of the embodiment of the present invention to scale up or down the content of each component according to the description of the embodiment of the present invention. Specifically, the mass described in the description of the embodiments of the present invention may be a mass unit known in the chemical industry field, such as μ g, mg, g, and kg.
During the research process, the inventor finds that the lithium ions have a safe bone/cartilage generation promoting function. Therefore, the embodiment of the invention provides a biological composite material, a preparation method and application thereof, wherein the biological composite material has the safe bone/cartilage generation promoting functional characteristic around lithium ions.
In one aspect, embodiments of the present invention provide a biocomposite material. The biological composite material comprises a biological compatible material and an effective dose of bone growth promoting agent, and the bone growth promoting agent is dispersed in the biological compatible material.
Wherein the bone growth promoting agent contained in the biocomposite material comprises a lithium source providing lithium ions. Thus, the biocomposite material uses a lithium source providing lithium ions as a bone growth promoter, namely as a growth factor for bone or cartilage repair, and gives the biocomposite material excellent bone including cartilage repair ability with high safety; and because the lithium source has wide sources, low price, stable structure and physicochemical properties and small toxicity or side effect, the stability and safety of the function of promoting the generation of the bone/cartilage of the biological composite material are effectively improved, thereby reducing the cost. Therefore, the biological composite material effectively overcomes the defects of unsatisfactory stability, uncertain safety, limited source and high cost of the existing growth factors, particularly endogenous growth factors.
In addition, due to the characteristics of the biocomposite, the lithium source that provides lithium ions should be understood to be a medically acceptable lithium source. As in one embodiment, the lithium source providing lithium ions comprises at least one of lithium chloride, elemental lithium. The selected lithium sources not only have high safety and good stability, but also can realize the controllable release of stable lithium ions under the action of a biocompatible material carrier, thereby achieving the purpose of continuously promoting the growth and the repair of bones; in addition, the sources of the lithium sources are wide, and the cost is low.
Second, the bone growth promoting agent comprising the lithium source is present in the biocomposite in an effective amount, by "effective amount" is meant an amount effective to promote bone growth or repair, and by "effective amount" is meant an amount of bone growth promoting agent, particularly a lithium source that provides lithium ions, sufficient to exhibit a bone growth or bone repair benefit or clinical significance to the individual. One skilled in the art will appreciate that the actual amount or dosage of the bone growth promoting agent, particularly the lithium source that provides the lithium ions, will depend on the nature and severity of the damage to the bone, the age and general condition of the subject, and the like. As in one embodiment, the lithium source is present in the biocomposite in an amount of 1-15% by weight.
The biocompatible material contained in the biological composite material can be a biocompatible material commonly used in the field of bone repair, such as a degradable biocompatible material. In an embodiment, the biocompatible material may comprise at least one of a degradable polymer, a biomimetic apatite, a bioglass, an acellular bone matrix. The biocompatible materials have high biocompatibility and good biocompatibility with bones, and can effectively load the lithium source, regulate and control the sustained release of lithium ions of the lithium source, thereby realizing good and sustained promotion of bone growth and repair of the biocomposite.
In one embodiment, when the biocompatible material comprises a degradable polymer, the degradable polymer comprises one or a mixture of two of a medical natural polymer and a medical synthetic polymer; wherein, the medical natural polymer can comprise at least one of chitosan, sodium alginate and methyl cellulose; the medical synthetic polymer may include at least one of polylactide, polyglycolide, polyanhydride, polytrimethylene carbonate, polydioxanone, polycaprolactone, polylactic acid-glycolic acid copolymer, electrospun membrane, biodegradable fiber. In a particular embodiment, the degradable polymer has a weight average molecular weight of 3 to 20 ten thousand.
In one embodiment, when the biocompatible material comprises biomimetic apatite, the biomimetic apatite may comprise a mixture of one or both of calcium triphosphate or hydroxyapatite.
In each embodiment of the biocomposite material, the biocompatible material accounts for 85-99% of the total weight of the biocomposite material, and when the biocompatible material contains both a degradable polymer and a biomimetic apatite, the mass ratio of the degradable polymer to the biomimetic apatite is 9: 1-6: 4.
Therefore, the biocomposite material in the above embodiments provides a lithium source of lithium ions as a growth factor for bone or cartilage repair, imparts excellent bone including cartilage growth and repair ability to the biocomposite material, and has low toxicity or side effects, high safety, and low cost. And under the action of the biocompatible material, the sustained release of lithium ions of the lithium source can be regulated and controlled, so that the biological composite material can well and continuously promote the growth and repair of bones including cartilages.
On the other hand, on the basis of the above-mentioned biocomposite material, the embodiments of the present invention also provide a preparation method of the biocomposite material. The preparation method of the biological composite material of the embodiment of the invention is shown in figure 1, and comprises the following steps:
step S01, mixing a lithium source for providing lithium ions, components contained in a biocompatible material and a solvent to prepare slurry;
and S02, drying the slurry.
Specifically, the lithium source species and the biocompatible material in step S01 are the same as those in the biocomposite material described above, and are not repeated herein for brevity. The solvent may be a solvent commonly used for preparing the biocompatible material, such as in one embodiment, the solvent includes at least one of 1, 4-dioxane, water, ethanol, methanol, dimethyl sulfoxide, acetone, and Dimethylformamide (DMF).
In addition, the mixing ratio of the lithium source and the biocompatible material should be such that the lithium source is contained in an effective amount in the prepared biocomposite. The amount of the solvent should be sufficient to ensure that the lithium source is well mixed with the components of the biocompatible material.
The mixing manner of the lithium source and the biocompatible material can be conventional mixing manner, and any mixing processing manner which can sufficiently and uniformly mix the components to form uniform slurry is within the scope of the disclosure of the present invention. In one embodiment, the lithium source is mixed with the biocompatible material and the solvent as follows:
and mixing the components contained in the biocompatible material with a solvent, and adding the lithium source solution for mixing again.
By the mixing treatment mode, the components contained in the biocompatible material and the lithium source can be uniformly dispersed in the solvent to form uniformly and stably mixed slurry. The solvent in the solution of the lithium source may be a solvent that can dissolve the lithium source and is safe for medical use, and may be, but not limited to, water.
In step S02, the drying process is performed on the slurry to remove the solvent component in the slurry, and the lithium source has good stability, so the drying process can be performed by a drying method commonly used for biocompatible materials, such as freeze drying or oven drying. In addition, before the slurry is dried, the slurry can be firstly shaped according to the requirement, and a corresponding bracket can be directly formed after the slurry is dried.
Therefore, the method for preparing the biocomposite material mixes the lithium source for providing lithium ions with the components contained in the biocompatible material, and effectively ensures the stability of the lithium source as an active factor for promoting the growth and repair of bones including cartilage in the preparation process, thereby ensuring the function of stably promoting the generation of bones/cartilages of the prepared biocomposite material, and simultaneously endowing the prepared biocomposite material with high safety and low production cost.
On the basis of the biological composite material and the preparation method thereof, the embodiment of the invention also provides a biological scaffold, in particular an artificial bone scaffold. The biological scaffold comprises the biocomposite material described above or a biocomposite material prepared by the method of making the biocomposite material described above. In a specific embodiment, the slurry containing the biocomposite material described above can be formed by molding and curing the molded biocomposite material according to the requirements of a bone scaffold structure. Thus, since the bio-scaffold includes the bio-composite material according to the embodiment of the present invention, the bio-scaffold has a stable and safe bone/cartilage generation promoting function and is low in cost. In addition, the detection proves that the biological scaffold has a porous structure, the pore diameter is 300-600 mu m, and the porosity is 45-80%. Therefore, the biological scaffold has mechanical properties and structural characteristics close to those of bones.
The carbon/carbon composite material of the biocomposite according to the embodiments of the present invention and the method for preparing the same are illustrated by various embodiments.
Example 1
The embodiment provides a biological composite material and a preparation method thereof, wherein the biological composite material comprises polylactic acid-glycolic acid copolymer (PLGA), β calcium phosphate (TCP) and lithium chloride, the mass ratio of the PLGA to the TCP to the lithium chloride is 4.368: 1.092: 0.273, the PLGA (polylactic acid-glycolic acid copolymer) is purchased from Shandong province medical instrument research institute, the molecular weight of the PLGA is 10 ten thousand, the molar ratio of lactic acid to glycolic acid is 70:30, the TCP is purchased from Beijing modern Oriental Fine chemical products, Inc., the lithium chloride is purchased from Sigma, the purity is more than 99%, and a rapid molding machine of the biological material is developed by the mechanical engineering system of Qinghua university and has the model number of CLRF-2000-II.
The preparation method of the biological composite material comprises the following steps:
s11: 092g of TCP was placed in a 15ml centrifuge tube and 10ml of 1, 4-dioxane (C) was added4H8O2) Ultrasonically treating for 30min, weighing 4.368g PLGA, placing in a small beaker of 50ml, pouring the solution containing TCP, and stirring overnight at room temperature;
s12: adding 27.3mg of lithium chloride into 1mL of water for dissolving to prepare a lithium chloride solution;
s13: adding the lithium chloride solution obtained in the step S12 into the solution obtained in the step S11, and uniformly stirring for 1 hour to obtain slurry containing PLGA, TCP and lithium chloride;
s14: adding the slurry obtained in the step S13 into a 3D printing material tank, installing the tank on a machine, fixing, and adjusting the temperature of a forming material to 18-30 ℃ below zero; computer control and forming: opening software Cark, calling in method, setting instrument parameters (nozzle scanning speed 15-23mm/s, nozzle scanning filling speed 0.9-1.5, aperture 1mm, layer height 0.12mm), and making into 2.4 × 2.4 × 2.4cm without changing other parameters3And then the shaped blocks were directly freeze-dried for 48 hours to obtain the bioscaffold shown in fig. 2.
Example 2
The present example provides a biocomposite material and a method of making the same. The biological composite material comprises a lactic acid-glycolic acid copolymer (PLGA) and lithium chloride, wherein the mass ratio of the PLGA to the lithium chloride is 75: 5. PLGA (polylactic-co-glycolic acid) is purchased from institute of medical devices in Shandong province, and has a molecular weight of 10 ten thousand, wherein the molar ratio of lactic acid to glycolic acid is 50: 50; TCP was purchased from Beijing, modern Oriental Fine chemical products, Inc.; lithium chloride was purchased from Sigma with a purity greater than 99%; and the biomaterial rapid prototyping machine is developed by the mechanical engineering system of Qinghua university, and has the model of CLRF-2000-II.
The preparation method of the biological composite material comprises the following steps:
s21: weighing 3.75g of PLGA, placing the PLGA in a small 50ml beaker, pouring the solution containing the TCP, and stirring the mixture at room temperature overnight;
s22: adding 250mg of lithium chloride into 10mL of water for dissolving to prepare a lithium chloride solution;
s23: adding the lithium chloride solution obtained in the step S22 into the solution obtained in the step S11, and uniformly stirring for 1 hour to obtain slurry containing PLGA and lithium chloride;
s24: adding the slurry obtained in the step S23 into a 3D printing material tank, installing the tank on a machine, fixing, and adjusting the temperature of a forming material to 18-30 ℃ below zero; computer control and forming: opening software Cark, calling in method, setting instrument parameters (nozzle scanning speed 15-23mm/s, nozzle scanning filling speed 0.9-1.5, aperture 1mm, layer height 0.12mm), and making into 2.4 × 2.4 × 2.4cm without changing other parameters3And then the molded block was directly freeze-dried for 48 hours to obtain a bioscaffold.
Example 3
The present example provides a biocomposite material and a method of making the same. The biological composite material comprises biodegradable fiber, hydroxyapatite and element lithium, wherein the mass ratio of the biodegradable fiber to the hydroxyapatite to the element lithium is 5: 2: 1.
the biocomposite preparation method the biocomposite of this example was prepared by referring to the preparation method in example 1.
Comparative example 1
This comparative example provides a biocomposite, with reference to example 1, without lithium ion scaffold PLGA/TCP.
Correlation performance testing
The biocomposites provided in examples 1-3 and comparative example 1 were subjected to bone repair experiments as follows:
the experimental method comprises the following steps: after anaesthesia, New Zealand white rabbits (2.7-3.0kg,5-6months) were anesthetized, the articular cavity was exposed, a hole was drilled downward perpendicular to the cartilage surface at the center of the distal femoral trochlear with an electric drill for orthopedic surgery, the hole diameter was 3.2mm, and the depth was 3mm, and a defect area was prepared. Thereafter, the wound was sutured without implanting a stent as a control group, without implanting a drug-containing stent as a blank stent group as provided in comparative example 1, and with lithium chloride stent group as provided in example 1. Injecting xylenol orange (90mg/kg) and calcein (10mg/kg) subcutaneously for 14 days and 7 days before the sacrifice, taking the femur, fixing, performing micro-CT scanning, and embedding hard tissue sections.
Examples 2-3 provide experimental parameters for bone repair of biocomposites as described in example 1 above.
The results are as follows:
the experimental results are as follows: the micro-CT scanning photograph is shown in FIG. 3, wherein FIG. 3-A is a control group micro-CT photograph, FIG. 3-B is a blank stent group micro-CT photograph, FIG. 3-C is a lithium chloride stent group micro-CT photograph, and the shaded portion in FIG. 3 is a bone defect region, and the white region is a new bone region. From the results of the micct pictures, it can be seen that the lithium chloride stent promotes the bone mass of new bone formation at the defect, and is significantly superior to the PLGA/TCP stent in comparative example 1. Further experimental tests on the bone repair of the biocomposite in examples 2-3 revealed that the micro-CT images of the scaffolds of the biocomposite group of experimental mice provided in examples 2-3 are similar to those of FIG. 3-C, and therefore, the biocomposite provided in examples 2-3 can also promote the amount of new bone formation in the defect. Therefore, it is understood from the experimental results that the biocomposite material provided in the examples of the present invention has a function of effectively promoting bone/cartilage formation and is highly safe.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims (10)

1. A biocomposite material comprising a biocompatible material, wherein: further comprising an effective amount of a bone growth promoting agent, and the bone growth promoting agent is dispersed in the biocompatible material; wherein the bone growth promoter includes a lithium source providing lithium ions.
2. The biocomposite material of claim 1, wherein: the lithium source includes at least one of lithium chloride and elemental lithium.
3. The biocomposite material of claim 1 or 2, wherein: the weight percentage of the lithium source in the biological composite material is 1-15%.
4. The biocomposite material of claim 1 or 2, wherein: the biocompatible material comprises at least one of degradable polymer, bionic apatite, bioglass and acellular bone matrix.
5. The biocomposite material of claim 4, wherein: the degradable polymer comprises one or a mixture of two of medical natural polymer and medical synthetic polymer;
the bionic apatite comprises one or two of calcium triphosphate or hydroxyapatite.
6. The biocomposite material of claim 5, wherein: the medical natural polymer comprises at least one of chitosan, sodium alginate and methyl cellulose;
the medical synthetic polymer comprises at least one of polylactide, polyglycolide, polyanhydride, polytrimethylene carbonate, polydioxanone, polycaprolactone, polylactic acid-glycolic acid copolymer, electrostatic spinning membrane and biodegradable fiber.
7. The preparation method of the biological composite material is characterized by comprising the following steps:
mixing a lithium source for providing lithium ions, components contained in a biocompatible material and a solvent to prepare slurry;
and drying the slurry.
8. The method of claim 7, wherein the lithium source is mixed with a biocompatible material and a solvent as follows:
and mixing the components contained in the biocompatible material with a solvent, and adding the lithium source solution for mixing again.
9. The production method according to claim 7 or 8, characterized in that: the solvent comprises at least one of 1, 4-dioxane, water, ethanol, methanol, dimethyl sulfoxide, acetone and dimethylformamide.
10. A bioscaffold, comprising: the material of the biological scaffold comprises the biological composite material of any one of claims 1 to 6 or the biological composite material prepared by the preparation method of any one of claims 7 to 9.
CN201811216198.1A 2018-10-18 2018-10-18 Biological composite material, preparation method thereof and biological scaffold Pending CN111068122A (en)

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