CN116251235A - Porous osteoconductive/inducible self-curing calcium phosphate composite material and its preparation method - Google Patents

Abstract

The invention belongs to the technical field of materials and instruments for clinical application in stomatology, and relates to a porous osteoconductive/induced self-curing calcium phosphate composite material and a preparation method thereof. The preparation method comprises the following steps: 1), medical gelatin sponge or collagen sponge Pulverize and make the sponge particle that particle diameter is 0.1-2mm; 2), the powder of described sponge particle and self-curing calcium phosphate is uniformly mixed together and form mixture standby; 3), the liquid of described self-curing calcium phosphate Add the mixture, mix it evenly, and form a paste; 4) After the paste is cured, a porous osteoconductive/bone-induced self-curing calcium phosphate re-examination material is obtained. It can improve the efficiency of material guidance/induction of bone regeneration, the reliability and convenience of clinical application of materials, etc., and is suitable for the regeneration and repair of bone defects in different parts/sizes, and is suitable for composite application with local oral antibacterial drugs.

Description

Porous osteoconductive/inducible self-curing calcium phosphate composite material and its preparation method

technical field

The invention belongs to the technical field of materials and devices for clinical application in stomatology, and relates to a preparation method of a guiding/inducing bone regeneration material/device, in particular to a porous bone guiding/inducing self-curing calcium phosphate composite material and a preparation method thereof.

Background technique

Alveolar bone/jaw bone defects caused by various odontogenic inflammations, tumors and oral and maxillofacial trauma are the most common diseases in the field of stomatology, which will seriously affect the integrity and appearance of oral dentition, resulting in impaired oral mastication and language functions even facial deformities.

The current main clinical techniques for repairing alveolar bone/jaw defects include autologous bone grafting, implantation of bone substitute materials into bone defects, and bioguiding membranes to protect bone defects. Autologous bone transplantation is still the most ideal method for repairing bone defects, but the transplantation operation is more complicated, with higher technical requirements, additional damage to the bone donor site, common causes of bone graft failure due to postoperative infection and other reasons, and great losses to patients. Therefore, using artificial materials instead of autologous bone grafts to repair bone defects and reconstruct bone structure is an important research direction of contemporary medicine.

Artificial materials mainly repair bone defects through the mechanism of guiding/inducing bone regeneration, that is, after the material is implanted in the body, it gradually degrades, and at the same time guides/induces stem cell differentiation, osteoblast proliferation, angiogenesis and ingrowth in the surrounding bone tissue to form new bone defects. Bone tissue replaces the original material to achieve bone regeneration. The commonly used artificial bone conduction/induction materials are mostly granular, which is convenient for implantation into irregular bone cavities, but has no load-bearing capacity, and the degree of packing density varies during implantation, which will affect its internal porosity and guided bone regeneration efficiency. In addition, it is generally required to be used together with the bioguiding membrane, and the barrier function of the biofilm is used to protect the bone graft particles from loss, and at the same time prevent the growth of fast-growing fibroblasts or epithelial cells in the surrounding soft tissue, and avoid their interference with growth. Slow proliferation and regeneration of osteoblasts and blood vessels to obtain ideal bone regeneration effect. These problems have affected the scope of application, convenience and reliability of clinical application of granular artificial bone graft materials.

Therefore, in view of the obvious shortcomings of existing bone regeneration clinical materials, it is urgent to develop a new type of porous osteoconductive/inductive composite material for stomatology and its preparation method.

Contents of the invention

The purpose of the present invention is to overcome the shortcomings existing in the existing materials, to provide a porous bone conduction/induced self-curing calcium phosphate composite material and its preparation method, which can improve the efficiency of material guidance/induced bone regeneration and the reliability of the clinical application of the material It is suitable for regenerative repair of bone defects in different parts/sizes, and it is also suitable for compound application with local oral antibacterial drugs.

In order to achieve the above object, the present invention provides the following technical solutions:

A method for preparing a porous osteoconductive/inducible self-solidifying calcium phosphate composite material, characterized in that it comprises the following steps:

1), crush medical gelatin sponge or collagen sponge to make sponge particles with a particle size of 0.1-2mm;

2), the powder of described sponge particle and self-curing calcium phosphate is uniformly mixed together to form a mixture;

3), adding the liquid agent of self-curing calcium phosphate into the mixture, forming a paste after mixing evenly;

4) After the paste is cured, a porous bone-conducting/bone-inducing self-curing calcium phosphate composite material is obtained.

Preferably, in the step 2), when mixing, the mass ratio of the volume of the sponge particles to the self-curing calcium phosphate powder is in the range of 1-2 cm ³ /g.

Preferably, in the step 3), the ratio of the volume of the self-curing calcium phosphate liquid to the mass of the self-solidifying calcium phosphate powder in the mixture is in the range of 0.3-0.5ml/g.

Preferably, the medical gelatin sponge or collagen sponge powder is a gelatin sponge or collagen sponge for routine clinical hemostasis.

Preferably, the self-curing calcium phosphate powder is medical self-curing calcium phosphate artificial bone.

Preferably, in the step 1), the medical gelatin sponge or collagen sponge is pulverized by using a wall breaking machine or a tissue homogenizer.

Preferably, the liquid agent of self-curing calcium phosphate is water or a solution containing calcium or phosphate.

In addition, the present invention also provides a porous osteoconductive/inducible self-solidifying calcium phosphate composite material, which is characterized in that it is prepared by the above method.

Compared with the prior art, the porous osteoconductive/inducible self-solidifying calcium phosphate composite material and its preparation method of the present invention have one or more of the following beneficial technical effects:

1. The present invention realizes the simultaneous use of two clinical materials/devices for the first time, improves the efficiency of guiding/inducing bone regeneration, and has unique advantages in the convenience, reliability, economy, applicability and other aspects of clinical application.

2. The porous osteoconductive/induced self-curing calcium phosphate composite material prepared by the present invention has high porosity, uniform distribution of pores, self-consolidation of the material, sufficient plasticity before consolidation, good strength after consolidation, and can absorb It is stable and the absorption and degradation time is equivalent to that of cancellous bone. It is convenient to use, simple to operate, and reliable to maintain bone regeneration space. It is suitable for guided/induced bone regeneration treatment of various simple or complex bone defects or bone cavities.

3. The porous osteoconductive/inducible self-curing calcium phosphate composite material prepared by the present invention can be used in combination with commonly used clinical dental antibacterial drug preparations, such as compounding with minocycline, to achieve antibacterial drug loading. Gradually degraded, it can continuously and slowly release minocycline with anti-infection and bone regeneration-inducing effects, effectively avoid local infection, reduce the interference of bacterial environment on the bone regeneration process, and improve the effect and success rate of guided bone regeneration to repair bone defects.

Detailed ways

The present invention will be further described below in conjunction with the examples, and the contents of the examples are not intended to limit the protection scope of the present invention.

Self-solidifying calcium phosphate (Calcium phosphate cement, CPC) has unique advantages in the construction of composite biomaterials. CPC, also known as calcium phosphate bone cement, is stored separately in solid-phase powder and liquid-phase liquid. The powder is a mixture of several calcium phosphate salts, including tetracalcium phosphate (TTCP), anhydrous Calcium hydrogen phosphate (DCPA), etc., when used, mixed with liquid agent, that is, water or an aqueous solution with other components, can undergo a chemical reaction and self-cure. The curing reaction is mild, and it can be mixed and cured with various organic components very conveniently. During the curing process, it can be shaped freely, and after curing, it will form a material with hydroxyapatite crystals as the main component, which can bear a certain load, has guiding osteogenic activity and good biocompatibility, and does not require the barrier and protection of a biological guiding film It is an important material in bone regeneration research and clinical application, and it is an ideal inorganic carrier for bioactive molecules. However, the composition, structure, and function of simple CPC materials and natural bone matrix still have a large gap. The main problems include: low curing porosity, no ability to mobilize and induce cell differentiation, and slow degradation and transformation in vivo.

Gelatin or collagen sponge is made from the extracellular matrix of animal skin/bone and other tissues through different physical and chemical processes. It has various functions such as hemostasis, support, protection, and connection tissue healing. Tissue cells and growth factors have good affinity. Medical gelatin and collagen are routine clinical hemostatic materials with outstanding biodegradability, cheap price, safety and reliability.

If the gelatin/collagen is combined with the self-curing calcium phosphate material, the gelatin/collagen sponge can form a pore structure inside the self-curing calcium phosphate material, which is conducive to the penetration of tissue fluid/oxygen/cells, etc., and is conducive to guiding/inducing bone regeneration; and, both Mixing basically does not affect the plasticity of the material, which is convenient for filling irregular bone defects or bone regeneration spaces; at the same time, it can form a stable scaffold structure after curing, which can withstand a certain load, and is expected to be used for immediate or early implant implants Body surface coating, alveolar ridge extraction socket site preservation, alveolar bone/jaw bone defect filling and other clinical treatment processes; the material can be in close contact with the surrounding bone, and the contact area is wide, and the bone conduction effect is strong; solid material Less loss, self-consolidation after filling, stable porosity, less affected by clinical operations; no need for combined application with biofilm guidance technology, reducing medical expenses and facilitating clinical operations.

In addition, the oral environment is a bacterial environment. It is often difficult to completely isolate and seal alveolar bone/jaw bone defects from the oral environment. Bacteria have a significant adverse effect on the guided bone regeneration process, which can lead to prolonged healing time and even lead to postoperative infection. Failed bone defect repair. The slow-release carrier capability of CPC enables it to be combined with oral antibacterial drugs to achieve sustained and sustained release of antibacterial ability and improve the anti-inflammatory and anti-infective properties of the material.

Based on this, the inventors have invented a porous bone-conducting/inducing self-curing calcium phosphate composite material and its preparation method, which uses medical gelatin sponge or collagen sponge combined with self-curing calcium phosphate material, which can improve material guiding/inducing bone regeneration The efficiency, reliability and convenience of clinical application of materials, etc., are suitable for the regenerative repair of bone defects in different parts/sizes, and are suitable for compound application with local oral antibacterial drugs.

Specifically, the preparation method of the porous osteoconductive/induced self-curing calcium phosphate composite material of the present invention comprises the following steps:

1. Crush the medical gelatin sponge or collagen sponge to make sponge particles with a particle size of 0.1-2mm.

Wherein, the medical gelatin sponge or collagen sponge powder can be gelatin sponge or collagen sponge for routine clinical hemostasis.

Preferably, when pulverizing, a wall breaking machine or a tissue homogenizer can be used to pulverize the medical gelatin sponge or collagen sponge into small particles of uniform size.

2. The sponge particles and the powder of self-curing calcium phosphate are evenly mixed together to form a mixture.

The self-curing calcium phosphate consists of powder and liquid. The powder includes a variety of calcium phosphate compounds. The liquid is water or a solution containing calcium or phosphate. The two are mixed to form a paste, which can undergo a chemical reaction and gradually condense and harden into a solid. The final product produced is brushite (dihydrate dicalcium phosphate) or apatite (hydroxyapatite or calcium-deficient hydroxyapatite).

Preferably, the self-curing calcium phosphate powder is medical self-curing calcium phosphate artificial bone.

In the present invention, when mixing, the mass ratio of the volume of the sponge particles to the self-curing calcium phosphate powder ranges from 1 to 2 cm ³ /g. That is, every 1-2cm ³ of the sponge particles are uniformly mixed with 1g of the self-curing calcium phosphate powder. After a large number of medical experiments, it is found that mixing in this ratio can help ensure the porosity of the prepared composite material, and can make the prepared composite material have sufficient support.

3. Add the liquid agent of self-curing calcium phosphate into the mixture, mix well and form a paste.

Preferably, the liquid agent of self-curing calcium phosphate is water or a solution containing calcium or phosphate.

In addition, the ratio of the volume of the self-solidifying calcium phosphate liquid to the mass of the self-solidifying calcium phosphate powder in the mixture is in the range of 0.3-0.5ml/g. That is, when adding the liquid, 0.3-0.5 ml of the liquid is added to the mixture containing 1 g of the powder. After a large number of medical experiments, it was found that mixing with this ratio can help the curing of the prepared composite material.

4. After the paste is solidified, a porous bone-conducting/bone-inducing self-curing calcium phosphate composite material is obtained.

During the curing process, a chemical reaction occurs to harden the material, and a large number of degradable gelatin/collagen sponge particles are evenly distributed inside it to realize the formation of pores.

In the present invention, the paste can be implanted into a bone defect or a physiological or pathological bone cavity with a syringe, a periosteal stripper, or a dental tampon, and packed to make it tightly bonded to the surrounding bone wall, and then the paste can be self-sufficient in situ. Solidification, that is, porous osteoconductive/induced self-curing calcium phosphate composites can be obtained at bone defects/bone cavities.

Furthermore, in the present invention, the paste can be mixed with dental minocycline hydrochloride ointment, and then implanted into the bone defect cavity. In this way, through the combined application of clinically used dental antibacterial drug preparations, such as compounding with minocycline, antibacterial drug loading can be realized. After implantation in the body, the material will gradually degrade, and the anti-infection and bone regeneration-inducing effects can be continuously and slowly released. Minocycline can effectively avoid local infection, reduce the interference of the bacterial environment on the bone regeneration process, and improve the effect and success rate of guided bone regeneration to repair bone defects.

The above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the implementation of the present invention. For those of ordinary skill in the art, other changes or changes in different forms can be made on the basis of the above description. All the implementation manners cannot be exhaustively listed here. All obvious changes or variations derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims (8)

1. A method for preparing a porous bone guiding/inducing self-curing calcium phosphate composite material, which is characterized by comprising the following steps:

1) Crushing medical gelatin sponge or collagen sponge to obtain sponge particles with the particle size of 0.1-2 mm;

2) Uniformly mixing the sponge particles with the powder of the self-curing calcium phosphate to form a mixture;

3) Adding the liquid agent of self-curing calcium phosphate into the mixture, and uniformly mixing to form paste;

4) And curing the paste to obtain the porous bone guiding/induced bone self-curing calcium phosphate composite material.

2. The method for preparing a porous bone guiding/inducing self-curing calcium phosphate composite material according to claim 1, wherein in the step 2), the mass ratio of the volume of the sponge particles to the powder of the self-curing calcium phosphate is in the range of 1-2cm at the time of mixing ³ /g。

3. The method of preparing a porous bone guiding/inducing self-setting calcium phosphate composite according to claim 2, wherein in the step 3), the ratio of the volume of the liquid of self-setting calcium phosphate to the mass of the powder of self-setting calcium phosphate in the mixture is in the range of 0.3-0.5ml/g.

4. The method for preparing a porous bone conduction/induction self-curing calcium phosphate composite material according to claim 3, wherein the medical gelatin sponge or collagen sponge powder is a clinically conventional hemostatic gelatin sponge or collagen sponge.

5. The method for preparing a porous bone conduction/induction self-curing calcium phosphate composite material according to claim 4, wherein the powder of self-curing calcium phosphate is medical self-curing calcium phosphate artificial bone.

6. The method for preparing a porous bone guiding/inducing self-curing calcium phosphate composite according to claim 5, wherein in the step 1), a wall breaking machine or a tissue refiner is used to break up the medical gelatin sponge or the collagen sponge.

7. The method of preparing a porous bone conduction/induction self-curing calcium phosphate composite material according to claim 6, wherein the liquid agent of self-curing calcium phosphate is water or a solution containing calcium or phosphate.

8. A porous osteoconductive/inductive self-curing calcium phosphate composite material, characterized in that it is prepared by the method according to any one of claims 1-7.