CN114425104B - Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof - Google Patents
Medicine-carrying bone guiding/inducing composite structure and preparation method and application thereof Download PDFInfo
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/028—Other inorganic materials not covered by A61L31/022 - A61L31/026
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/005—Ingredients of undetermined constitution or reaction products thereof
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/044—Collagen
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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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
- 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
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
Abstract
The invention relates to a drug-loaded bone guiding/inducing composite structure, a preparation method and application thereof, wherein the preparation method comprises the following steps: 1) Directly or indirectly dissolving the antibacterial drug in the medical gel to form drug-loaded medical gel; 2) Uniformly spreading artificial bone particles with the size of 0.2-1.5mm and the thickness of 0.2-1.5mm, and then coating or spraying medicine-carrying medical adhesive on the surface; 3) Flatly pressing the collagen membrane on the surface of the medicine-carrying medical glue, and gluing the collagen membrane and the artificial bone granular layer into a composite structure; 4) And after the medicine-carrying medical glue is dried and solidified, treating one side surface of the artificial bone particles of the composite structure, removing the medicine-carrying medical glue infiltrated on the surface layer, and exposing the artificial bone particles to obtain the medicine-carrying bone guiding/inducing composite structure. The bone regeneration guiding and inducing device can improve the convenience of material application, the stability of implantation in vivo and the reliability of guiding/inducing bone regeneration, and is suitable for the regeneration of bone defects of different parts/sizes or the protection and stability of comminuted fracture blocks.
Description
Technical Field
The invention belongs to the technical field of oral medical clinical application materials and instruments, and relates to a preparation method of a guiding/inducing bone regeneration material/instrument, in particular to a drug-loaded bone guiding/inducing composite structure and a preparation method and application thereof.
Background
Jaw/alveolar bone defects caused by inflammation, tumor, trauma are common diseases in the field of oral medicine, and can seriously affect the integrity and beauty of dentition, oral chewing and speech functions, even facial appearance and the like.
The current clinical treatment of jaw/alveolar bone defects mainly comprises autologous bone transplantation, implantation of bone substitute materials into bone defects, covering of membrane materials to protect bone defects and the like. At present, autologous bone grafting is still the most ideal means for repairing bone defects, but the grafting operation is more complex, the technical requirement is higher, the bone supply area has additional damage, and once the bone grafting fails due to postoperative infection and other reasons, the loss is also larger. Therefore, the adoption of artificial materials to replace autologous bone transplantation for repairing bone defects and reconstructing bone structures is an important research direction in modern medicine.
The artificial material realizes bone defect repair mainly through a guiding/inducing bone regeneration mechanism, and can be divided into two technical implementation modes of membrane guiding bone regeneration and scaffold guiding/inducing bone regeneration in clinical application. The membrane guided bone regeneration is to cover the bone defect lacuna or a bone regeneration space established by an operation by using a biological barrier membrane, prevent fibroblasts or epithelial cells which grow faster in peripheral soft tissues from growing in, ensure the proliferation and the regeneration of osteoblasts and blood vessels which grow slower, and realize the bone regeneration. The scaffold guides/induces the bone regeneration, which is to fill bone defects with bone substitute materials or perform incremental surgery on the bone surface as a scaffold to maintain an osteogenic space, wherein the scaffold materials can be gradually degraded, and simultaneously guide/induce stem cell differentiation, osteoblast proliferation and angiogenesis in peripheral bone tissues to grow into the surrounding bone tissues to form new bone tissues to substitute original materials, so that the bone regeneration is realized. To achieve the desired bone regeneration effect, membrane-guided bone regeneration is often used in combination with scaffold-guided/induced bone regeneration.
Existing biological barrier membranes used for membrane-guided bone regeneration include both non-absorbable and absorbable membranes. The non-absorbable membrane is usually made of polytetrafluoroethylene, metal titanium and the like, has high strength and plasticity, can reliably maintain an osteogenesis space, is retained by screws in use, needs to be taken out in a secondary operation, has large wound, and is generally used for complex bone defect repair or bone augmentation operations. The absorbable membrane is a collagen membrane obtained by carrying out physiological and biological treatment on xenogeneic/xenogeneic tissues such as dermis, pericardium and the like, or a membrane made of artificially synthesized collagen fiber, or a degradable material membrane made of high polymer, can be automatically degraded and absorbed/discharged after being implanted into a body, does not need to be taken out by secondary operation, but is often insufficient in strength, more flexible, and less in plasticity, and difficult to independently support and maintain an osteogenic space, and has higher requirements on operation skills because the membrane is smooth and difficult to retain. In addition, it is also common that the membrane degrades too rapidly, leading to premature barrier loss and affecting the bone regeneration effect.
The existing bone substitute materials for guiding/inducing bone regeneration of the scaffold generally use calcium phosphate crystal which is a basic component of bone inorganic substances as a main body, can be obtained by processing of xenogeneic/xenogeneic bone calcination and the like, or are natural or artificially synthesized hydroxyapatite, beta-tricalcium phosphate and often granular materials, so that irregular bone defects or bone regeneration spaces can be conveniently filled, and infiltration of tissue fluid, oxygen, cells and the like is facilitated, and the important defect is that the scaffold structure which is difficult to form stable retention is singly used, the scaffold structure is required to be combined with a membrane guiding technology for application, and common problems such as insufficient tightness of filling and loss of guiding effect caused by material loss are solved; or the filling is too tight, which affects the tissue fluid/oxygen/cell penetration, and further the material is difficult to degrade in time, which affects the bone regeneration and replacement. In order to solve the stability problem of granular materials, some bone guiding/inducing materials are prepared into lumps or curable sticky lumps and pastes, such as self-curing calcium phosphate bone cement, but the materials have the problems of too few/too small internal pores, poor body fluid permeability, too slow material degradation, difficult growth of osteoblasts and blood vessels into the materials, poor bone guiding/inducing effect and the like.
In order to solve the problems and improve the performance of the bone guiding/inducing material, some clinical products press/adhere granular bone replacing materials and fibrous collagen materials into block-shaped composite bone guiding/inducing materials, after the bone guiding/inducing materials are implanted into a body, collagen fibers are degraded quickly, more/larger pores can be formed in the materials, the bone guiding/inducing regeneration capacity is good, and blood/tissue fluid/osteoblasts can grow in the materials. However, such composites also have some significant disadvantages, such as: lack of plasticity and poor morphological adaptability to irregular bone defects; when the filling force is too large, the block materials are easily dispersed into granular materials, so that the retention of the materials is unstable and the materials are lost, and therefore, when the bone defect is large or irregular, the combined membrane guide materials and the technology are required to be applied together; the material price is expensive, and the clinical use is influenced.
In addition, the oral environment is a bacterial environment, the alveolar bone defect of the jaw bone is difficult to completely isolate and seal from the oral environment, bacteria have a relatively obvious adverse effect on the process of guiding bone regeneration, and the healing time can be prolonged or even postoperative infection can be caused, and the bone defect repair fails. The existing material lacks effective antibacterial drug loading and local slow release capability.
Therefore, in view of the obvious defects of the existing bone regeneration clinical material, the development of a novel medicament-carrying composite bone guiding/inducing structure for the department of stomatology and a preparation method thereof are urgently needed.
Disclosure of Invention
The invention aims to overcome the defects of the existing materials and provides a drug-loaded bone guiding/inducing composite structure, a preparation method and application thereof, which can improve the convenience of application of the bone guiding/inducing structure, the stability of the bone guiding/inducing structure in an implant and the reliability of bone regeneration induction and are suitable for the regeneration of bone defects of different positions/sizes or the protection and the stability of comminuted fracture blocks.
In order to achieve the above purpose, the invention provides the following technical scheme:
the preparation method of the medicine-carrying bone guiding/inducing composite structure is characterized by comprising the following steps of:
1) Directly or indirectly dissolving the antibacterial drug in the medical gel to form drug-loaded medical gel;
2) Uniformly spreading artificial bone particles with the size of 0.2-1.5mm and the thickness of 0.2-1.5mm, and then coating or spraying the medicine-carrying medical adhesive on the surface;
3) Flatly pressing a collagen membrane to the surface of the medicine-carrying medical glue, and gluing the collagen membrane and the artificial bone particles into a composite structure;
4) And after the medicine-carrying medical glue is dried and solidified, treating one side surface of the artificial bone particles of the composite structure, removing the medical glue infiltrated on the surface layer, and exposing the artificial bone particles to obtain the medicine-carrying bone guiding/inducing composite structure.
Preferably, the antibacterial drug is minocycline.
Preferably, the medical glue is polyacrylate.
Preferably, the artificial bone particles are natural or synthetic hydroxyapatite particles, or beta-tricalcium phosphate particles, or xenogeneic bone calcined particles.
Preferably, the artificial bone particles are spherical particles or irregular particles.
Preferably, the collagen membrane is xenogenic or xenogenic tissue-derived collagen membrane, or is an artificially synthesized collagen membrane.
Preferably, in the step 2), after the medicine-carrying medical glue is coated or sprayed on the surface, artificial bone particles with the size of 0.2-1.5mm are uniformly paved on the medicine-carrying medical glue, the thickness of the artificial bone particles is 0.2-1.5mm, and then the medicine-carrying medical glue is coated or sprayed on the surface.
In addition, the invention also provides a medicine-carrying bone guiding/inducing composite structure prepared by the method, which comprises a collagen membrane and artificial bone particles, and is characterized in that the artificial bone particles are fixed on the surface of the collagen membrane through medicine-carrying medical glue, the size of the artificial bone particles is 0.2-1.5mm, and the medicine-carrying medical glue is formed by dissolving antibacterial medicines in the medical glue.
The invention also provides an application method of the medicine-carrying bone guiding/inducing composite structure, which is characterized in that the medicine-carrying bone guiding/inducing composite structure is used as a barrier guiding film, so that the artificial bone particles on the medicine-carrying bone guiding/inducing composite structure face to a bone surface, are attached to the bone surface and cover the bone defect.
Finally, the invention provides an application method of the drug-loaded bone guiding/inducing composite structure, which is characterized in that the drug-loaded bone guiding/inducing composite structure is folded, laminated or wound into a roll to be used as a filling material to be implanted into a bone defect cavity.
Compared with the prior art, the medicine-carrying bone guiding/inducing composite structure, the preparation method and the application thereof have one or more of the following beneficial technical effects:
1. the invention realizes that a material/apparatus can be simultaneously used for membrane guidance and bracket guidance/bone regeneration induction for the first time, and has unique advantages in aspects of convenience, reliability, economy, applicability and the like of clinical application.
2. The sand paper-like bone guiding/inducing composite structure prepared by the invention has absorbability, properly prolongs the absorption and degradation time, obviously improves the strength and plasticity, retains the rough sand paper-like surface by means of friction force, is convenient to use, simple to operate, maintains reliable bone regeneration space, and is suitable for guiding/inducing bone regeneration treatment of various simple or complex bone defects or comminuted fractures.
3. The sand paper-like bone guiding/inducing composite structure described by the invention can form a three-dimensional bracket in various ways such as folding/laminating/winding, can fill various irregular gaps after being properly trimmed, can provide a certain bearing capacity, and is beneficial to the formation of internal blood clots and the ingrowth of osteoblasts and blood vessels due to the basic lamellar structure of the material, so that the basic bone regeneration healing process is promoted, and the sand paper-like uniformly distributed artificial bone particles ensure that each part has the largest contact area of interstitial fluid/oxygen/cells and the like, thereby avoiding the loss of the artificial bone particles, realizing the most effective bone regeneration guiding/inducing process, namely simultaneously realizing the membrane guiding and the bracket guiding bone regeneration effect on each part in the bone defect space.
4. The bone regeneration guiding/inducing structure can realize antibacterial drug loading by dissolving minocycline in medical glue, and after being implanted into a body, the minocycline with anti-infection and bone regeneration inducing effects can be continuously and slowly released along with the gradual degradation of materials, so that local infection is effectively avoided, the interference of a bacteria-containing environment on a bone regeneration process is reduced, and the effect and success rate of guiding bone regeneration and repairing bone defects are improved.
5. The invention utilizes collagen membrane, artificial bone particles, medical glue and minocycline to construct a sand paper-like composite structure, which purposefully improves the convenience of material application, the stability of implantation in vivo, the reliability of induced bone regeneration and the flexibility of being suitable for bone defects of different parts/sizes or comminuted fractures.
Detailed Description
The present invention is further illustrated by the following examples, which are not intended to limit the scope of the present invention.
The preparation method of the drug-loaded bone guiding/inducing composite structure comprises the following steps:
1. the antibacterial agent is directly or indirectly dissolved in the medical adhesive to form the drug-loaded medical adhesive.
In the invention, the medical glue is used as a biological adhesive for adhering the collagen membrane and the artificial bone particles. The medical glue comprises polyacrylate such as isobutyl cyanoacrylate, methyl cyanoacrylate and alkyl cyanoacrylate. The medical adhesive has no viscosity, toughness, slight elasticity, moderate hardness, difficult water solubility, no irritation or little irritation to human tissues, no toxicity, carcinogenesis, teratogenicity, decomposition in vivo, excretion and the like. Therefore, the medicine-carrying bone guiding/inducing composite structure is very suitable for preparing the medicine-carrying bone guiding/inducing composite structure.
Preferably, the antibacterial drug is minocycline. In the invention, minocycline and other medicines with anti-infection and bone regeneration inducing effects are compounded in the medical gel, so that sustained release is realized in the gradual degradation process of the medical gel, and the medical gel has good antibacterial effect and bone regeneration inducing effect.
More preferably, the concentration of the drug in the drug-loaded medical gel is 0.5-1 g/ml. That is, 0.5-1 g of the antibacterial agent is dissolved in 1 ml of the medical gel.
2. Uniformly spreading artificial bone particles with the size of 0.2-1.5mm, the thickness of 0.2-1.5mm, and coating or spraying medicine-carrying medical adhesive on the surface.
Wherein the artificial bone particles can be uniformly spread on a manufacturing plate or the like. And when the medicine-carrying medical glue is coated or sprayed, the coating or spraying thickness of the medicine-carrying medical glue is 0.3-0.5mm, so that the artificial bone particles and a subsequent collagen membrane are combined better.
Preferably, the artificial bone particles are uniformly laid in one to several layers. That is, after the medicine-carrying medical adhesive is coated or sprayed, artificial bone particles with the size of 0.2-1.5mm can be evenly spread on the medicine-carrying medical adhesive, and the thickness is 0.2-1.5mm. Then, medicine-carrying medical glue is coated or sprayed on the surfaces of the artificial bone particles. This may be repeated so as to have multiple layers of artificial bone granules.
The artificial bone particles are granular materials taking calcium phosphate as a main component, can be natural or synthetic medical hydroxyapatite particles, or medical beta-tricalcium phosphate particles, and can also be medical bone particles obtained by calcining, crushing and the like of the same or different bones.
Preferably, the particle size of the artificial bone particles is 0.2-1.5mm, and may be spherical particles or irregular particles. In the case of spherical particles, the diameter is 0.2 to 1.5mm. In the case of irregular particles, the maximum length in all directions is 0.2 to 1.5mm.
3. And flatly pressing a collagen membrane on the artificial bone particle layer coated or sprayed with the medical glue.
In the invention, the collagen membrane is derived from xenogeneic or xenogeneic tissues or is artificially synthesized.
4. After the medicine-carrying medical cement is fixed, one side surface of the artificial bone particles of the composite structure is treated by using methods such as organic solvent/sand blasting and polishing, the medical cement infiltrated on the surface layer of the artificial bone particles is removed, the artificial bone particles are exposed, and the medicine-carrying bone guiding/inducing composite structure is prepared.
Wherein the drug-loaded bone guiding/inducing composite structure is in a shape of sand paper.
In the invention, drugs such as minocycline and the like are dissolved in medical glue, coated or sprayed on the surface of a uniform and densely paved granular artificial bone material, then a collagen membrane is flatly pressed to a medical glue layer, after the medical glue is dried, the surface of one side of the artificial bone particles of the composite structure is processed by methods such as organic solvent/sand blasting and polishing, and the medical glue infiltrated on the surface layer is removed, so that the artificial bone particles are exposed, and a sand paper-like structure is formed. Because the dried medical glue and the artificial bone material glued on the surface of the membrane have certain strength and hardness, compared with a simple collagen membrane, the drug-loaded bone guiding/inducing composite structure has better strength, hardness and plasticity, and can be randomly trimmed according to the use position and the defect size.
In addition, the sand paper-like drug-loaded bone guiding/inducing composite structure can be divided into different models according to different diameters of artificial bone particles, is suitable for bone defects of different parts and sizes, is suitable for materials with smaller sand grains for bone defects with shallow surface and larger bone defects, and is suitable for composite materials with larger sand grains for bone defects with deeper parts and larger bone defects.
When in use, the drug-loaded bone guiding/inducing composite structure can be used as a guiding bone regeneration membrane to cover the surface of a bone defect lacuna or the surface of a bone regeneration area established by an operation. Wherein, the rough artificial bone particle surface is contacted with the bone surface, the formed friction force can ensure that the guiding membrane keeps stable retention on the bone surface, and meanwhile, the particle-shaped artificial bone material has stronger capability of guiding bone regeneration, can promote stem cell differentiation, osteoblast proliferation and blood vessel ingrowth and form a stable bone regeneration environment; the smooth collagen film surface is in contact with soft tissues such as peripheral mucoperiosteum and the like, so that the wound can be closed by pulling and suturing the soft tissues, meanwhile, the compact collagen film is used as a barrier, so that fibroblasts, epithelial cells and the like in the soft tissues can be prevented from entering a bone regeneration area, and the growth of osteoblasts, blood vessels and the like with low proliferation and regeneration speeds on the surface of the artificial bone granules is ensured; the three-layer structure (collagen membrane/medical glue/artificial bone particles) of the medicine-carrying bone guiding/inducing composite structure has better strength and certain plasticity, and is beneficial to supporting and maintaining bone defect or bone regeneration space morphology established by an operation; the antibacterial minocycline carried in the medical gel can be continuously and slowly released to a bone regeneration space along with the gradual degradation of the medical gel, so that the anti-infection effect is exerted, and the bone regeneration induction effect is achieved to promote bone regeneration activities.
During the use, this medicine carrying bone guide/induced composite construction still can form three-dimensional support through modes such as folding/range upon range of/reel, can regard as filling material after properly pruning, implants the bone regeneration space that bone defect inside or operation were established: all components of the material have degradability, and simultaneously have bone regeneration guiding/inducing effect, thereby being beneficial to stem cell differentiation, osteoblast proliferation and angiogenesis in peripheral bone tissues; the composite material three-dimensional support formed by folding/laminating/winding and other modes has better support strength, is beneficial to keeping bone defect or bone regeneration space shape established by operation, can increase the number of layers of folding/laminating/winding according to the bone bearing requirement of the defect part, and is suitable for the bone defect repairing requirements of different parts; sufficient space between the folded/laminated/rolled composite material sheets is beneficial to blood infiltration filling and blood clot formation, and further osteoblasts and vascular ingrowth, so that a good foundation is provided for subsequent bone regeneration activities; the uniformly paved and cemented artificial bone particles ensure that each part has the largest contact area of tissue fluid, oxygen, cells and the like, thereby avoiding the loss of the artificial bone particles, being beneficial to the penetration of nutrition and oxygen and providing favorable conditions for continuously and effectively guiding/inducing the bone regeneration activity; after the composite material three-dimensional scaffold which is folded/laminated/rolled in the bone defect or bone regeneration space is filled, a single-layer composite material film can be covered on the surface of the defect or bone regeneration area to provide barrier protection, and the scaffold guide/induction and the film guide bone regeneration can be stably repaired.
The above examples of the present invention are merely examples for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. Not all embodiments are exhaustive. All obvious changes and modifications which are obvious to the technical scheme of the invention are covered by the protection scope of the invention.
Claims (4)
1. The preparation method of the medicine-carrying bone guiding/inducing composite structure is characterized by comprising the following steps of:
1) Directly or indirectly dissolving the antibacterial drug in the medical gel to form drug-loaded medical gel; wherein the antibacterial drug is minocycline; the medical adhesive is polyacrylate;
2) Uniformly spreading artificial bone particles with the size of 0.2-1.5mm and the thickness of 0.2-1.5mm, and then coating or spraying the medicine-carrying medical adhesive on the surface; wherein the artificial bone particles are natural or synthetic hydroxyapatite particles, or beta-tricalcium phosphate particles, or xenogeneic bone calcined particles;
3) Flatly pressing a collagen membrane to the surface of the medicine-carrying medical glue, and gluing the collagen membrane and the artificial bone particles into a composite structure; wherein the collagen membrane is a xenogenesis or xenogenesis tissue derived collagen membrane, or is an artificial synthetic collagen membrane;
4) And after the medicine-carrying medical glue is dried and solidified, treating one side surface of the artificial bone particles of the composite structure, removing the medical glue infiltrated on the surface layer, and exposing the artificial bone particles to obtain the medicine-carrying bone guiding/inducing composite structure.
2. The method of claim 1, wherein the artificial bone particles are spherical particles or irregular particles.
3. The method for preparing the drug-loaded bone guiding/inducing composite structure according to claim 1, wherein in the step 2), after the drug-loaded medical glue is coated or sprayed on the surface, the artificial bone particles with the size of 0.2-1.5mm are uniformly spread on the drug-loaded medical glue with the thickness of 0.2-1.5mm, and then the drug-loaded medical glue is coated or sprayed on the surface.
4. A drug-loaded bone-guiding/inducing composite structure prepared by the method of any one of claims 1 to 3, comprising a collagen membrane and artificial bone particles, wherein the artificial bone particles are fixed on the surface of the collagen membrane by a drug-loaded medical glue, the size of the artificial bone particles is 0.2 to 1.5mm, and the drug-loaded medical glue is formed by dissolving an antibacterial drug in the medical glue.
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