阅读说明：本技术 镁基非晶-磷酸钙/硅酸钙复合填充物及其制备与应用 (Magnesium-based amorphous-calcium phosphate/calcium silicate composite filler and preparation and application thereof ) 是由 谭丽丽 杨柯 于 2019-04-04 设计创作，主要内容包括：本发明公开了一种具有高生物活性的镁基非晶-磷酸钙/硅酸钙复合填充物,包括：由复合磷酸钙盐/硅酸钙盐与镁基非晶粉末/纤维均匀混合得到的固相物质,以及由磷酸氢盐溶于水中得到的固化液。本发明还公开了一种可注射镁基非晶-磷酸钙/硅酸钙骨水泥及固态填充块的制备方法与应用：将固化液与固相物质混合均匀,调和形成糊状物,得到高生物活性的可注射镁基非晶-磷酸钙/硅酸钙骨水泥,用于制备骨组织创伤修复用可注射产品；将该骨水泥在体外进行固化、干燥,形成块状填充物,用于开放性骨缺损的填充。本发明原料成本低、制备方法简单、得到的镁基非晶-磷酸钙/硅酸钙复合填充物具有高的生物活性,并在体内可形成多孔结构,有利于组织修复。(The invention discloses a magnesium-based amorphous-calcium phosphate/calcium silicate composite filler with high bioactivity, which comprises the following components in part by weight: solid phase material obtained by uniformly mixing composite calcium phosphate salt/calcium silicate salt and magnesium-based amorphous powder/fiber, and solidified liquid obtained by dissolving hydrogen phosphate in water. The invention also discloses a preparation method and application of the injectable magnesium-based amorphous-calcium phosphate/calcium silicate bone cement and the solid filling block: uniformly mixing the curing liquid and the solid-phase substance, and blending to form a paste to obtain the injectable magnesium-based amorphous-calcium phosphate/calcium silicate bone cement with high bioactivity, which is used for preparing injectable products for repairing bone tissue wounds; the bone cement is cured and dried in vitro to form a block-shaped filler for filling open bone defects. The invention has low cost of raw materials and simple preparation method, and the obtained magnesium-based amorphous-calcium phosphate/calcium silicate composite filler has high bioactivity, can form a porous structure in vivo and is beneficial to tissue repair.)

1. A magnesium-based amorphous-calcium phosphate/calcium silicate composite filler with high bioactivity is characterized in that: the injectable calcium phosphate/calcium silicate filler is added with magnesium-based amorphous powder/fiber to form a composite filler.

2. The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler according to claim 1, wherein: the magnesium-based amorphous alloy comprises MgZnCaSr, wherein the Zn content is as follows: 21-40 at.%, the Ca content is: 2-7 at.%, Sr content: 0-5 at.%, balance Mg.

3. The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler according to claim 1, wherein: the magnesium-based amorphous powder/fiber content accounts for 1-30 wt% of the composite filler.

4. The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler according to claim 1, wherein: the magnesium-based amorphous powder is spherical or irregular, and the particle size is less than 1 mm.

5. The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler according to claim 1, wherein: the magnesium-based amorphous fiber has the length of 1-30mm and the width of 0.1-1 mm.

6. A method for preparing the magnesium-based amorphous-calcium phosphate/calcium silicate composite filler according to claim 1, comprising the steps of:

(1) mixing the calcium phosphate/calcium silicate bone cement solid-phase powder with the magnesium-based amorphous powder/fiber to obtain solid-phase composite powder;

(2) preparing a buffer solution with the equal molar concentration of 0.2-1.0 mol% of sodium dihydrogen phosphate and disodium hydrogen phosphate by using analytically pure or analytically pure sodium dihydrogen phosphate, a disodium hydrogen phosphate reagent and deionized water or distilled water as a curing solution;

(3) and (3) preparing the solid-phase composite powder prepared in the step (1) and the curing liquid prepared in the step (2) according to the solid-liquid ratio of 0.1-3: 1 to prepare the composite bone cement slurry.

7. The method for preparing the magnesium-based amorphous-calcium phosphate/calcium silicate composite filler according to claim 6, wherein: and (4) injecting the bone cement slurry prepared in the step (3) into a mold, curing for 20 minutes to 6 hours, and then drying at 80 to 100 ℃ to prepare the blocky filling material.

8. Use of a magnesium-based amorphous-calcium phosphate/calcium silicate composite filler prepared by the method of claim 6 for the preparation of injectable products for bone tissue wound repair.

9. Use of the magnesium-based amorphous-calcium phosphate/calcium silicate composite filler prepared by the method of claim 7 for preparing a filler for open bone defects.

Technical Field

The invention belongs to the technical field of preparation of medical bone filling materials, and particularly provides a magnesium-based amorphous-calcium phosphate/calcium silicate composite filler with high bioactivity, and a preparation method and application thereof.

Background

Bone defects caused by bone tumors, limb spinal deformity correction, severe bone trauma, osteoporosis, osteonecrosis and the like in clinic need to be reconstructed and treated by a bone grafting method. However, the limited availability of autogenous bone increases surgical trauma and the risk of immunological reactions and disease transmission in allogeneic bone limits its clinical use. Artificial bone implant materials have been the focus of bone tissue research, and applications that can replace autologous or allogeneic bone are desired. High porosity, degradability, high initial mechanical properties and good biological activity are essential conditions that bone repair materials must meet.

Calcium sulfate has been used in bone replacement materials for over 100 years and has proven to be safe and biocompatible. In 1980, Coetzee et al used calcium sulfate for 110 cases of defective skull and facial bone, and he concluded that calcium sulfate is an excellent substitute for bone graft, even comparable to bone graft itself. Calcium sulphate has then been criticized for its degradation before the new bone has not been fully inserted, and as a result calcium sulphate is used as a bone filling material, its degradation rate is too fast, and therefore calcium phosphate is used as a filler for bone defects and injectable calcium phosphate cements have been developed. Calcium Phosphate Cement (CPC), also known as Hydroxyapatite (HAC), is a self-setting non-ceramic hydroxyapatite artificial bone material first developed by Brown and Chow. The material has good biocompatibility, osteoconductivity, biosafety, arbitrary shaping and isothermality in the curing process, is a novel bone tissue repair and substitute material, receives wide attention of numerous scholars at home and abroad, and becomes one of the hot spots of research and application in the field of clinical tissue repair. CPC is prepared by mixing solid phase and liquid phase raw materials in a certain proportion into paste, implanting into a body, and crystallizing and solidifying in the in vivo environment. The chemical components of the final product after curing are similar to the inorganic components of bone tissues, the crystal phase structure of the final product is also similar to the bone tissues, the final product can be gradually degraded and absorbed after being implanted into bone defects, and calcium and phosphorus released by degradation participate in the formation of the bone tissues in the defect areas. The compression strength of the CPC final product is 36-55 MPa and is between that of cancellous bone and that of cortical bone. The magnitude of compressive strength is closely related to the particle size of the solid phase component used in the solidification process of CPC, the porosity of the final product and HA crystallinity, and the porosity of the final product is directly related to the powder-to-liquid ratio during mixing. The CPC with larger compressive strength is suitable for repairing bone defects of low-load parts, and the CPC with smaller compressive strength is suitable for repairing bone defects or small bone defects of non-load parts and filling root canals. However, the biological activity of CPC still needs to be improved in order to achieve better bone repair effect. Calcium Silicate (CS) -based materials have excellent bioactivity compared to calcium phosphate materials and have received increasing attention in recent years. A large number of researches prove that the CS-based material achieves the effect of quickly forming apatite deposition through the release of Si ions and can promote the formation and reconstruction of bone tissues. The self-setting CS bone cement has the advantage of low self-setting time, and exhibits good bone conductivity and the property of inhibiting inflammation of human dental pulp cells.

However, CPC and CS have several problems in that although they have a certain porosity, since the pore size is in the nanometer or submicron order, they lack macropores for promoting the growth of bone tissue, and not only osteocytes cannot grow in, but also interstitial fluid is difficult to permeate, and it is difficult to exert their osteoconductive effect; moreover, the degradation speed of the calcium silicate bone cement is too low relative to the growth speed of bone tissues, particularly, the degradation and absorption processes of the calcium silicate bone cement in vivo are carried out layer by layer, so that the absorption rate is low, the degradation is slow, and the generation and reconstruction of new bone tissues are hindered; in addition, the exertion of the biological activities of the two has the bone conduction effect, but the biological activities are exerted to a great extent by means of the biological active ions generated by the degradation of self materials, and the low degradation speed of the two makes the exertion of the biological activities insufficient to meet the clinical requirements, and particularly the biological activities are lower in the early stage of implantation.

Disclosure of Invention

In order to overcome the defects of the calcium phosphate/calcium silicate bone cement, the invention provides a preparation method of the calcium phosphate/calcium silicate bone cement and a block filler, which have high biological activity and can be degraded in vivo to form a hole. According to the characteristics that the degradation speed of the magnesium-based amorphous metal material in vivo is higher than that of a calcium phosphate bone cement material, magnesium ions with high biological activity are generated by degradation, and hydrogen is released while degradation, the magnesium-based amorphous metal powder/fiber and the calcium phosphate/calcium silicate powder are compounded, and the characteristic that the calcium phosphate/calcium silicate can be self-cured is utilized to prepare novel bone cement and a massive filling material which have higher biological activity, can be degraded in vivo to form holes, have high later degradation speed and are beneficial to the growth of new bone tissues. In addition, because the degradation speed of the magnesium-based amorphous alloy in vivo is lower than that of crystalline magnesium and the magnesium-based amorphous alloy, the problems of long solidification time and premature collapse in vivo of the composite material caused by high degradation speed of magnesium and the magnesium-based amorphous alloy can be avoided in the preparation process of the composite material.

The technical scheme adopted by the invention is as follows:

a magnesium-based amorphous-calcium phosphate/calcium silicate composite filler with high bioactivity is characterized in that: the injectable calcium phosphate/calcium silicate filler is added with magnesium-based amorphous powder/fiber to form a composite filler.

As a preferred technical scheme:

the magnesium-based amorphous alloy comprises MgZnCaSr, wherein the Zn content is as follows: 21-40 at.%, the Ca content is: 2-7 at.%, Sr content: 0-5 at.%, balance Mg.

The magnesium-based amorphous powder/fiber content accounts for 1-30 wt.% of the composite filler

The magnesium-based amorphous powder is spherical or irregular, and the particle size is less than 1 mm.

The magnesium-based amorphous fiber has the length of 1-30mm and the width of 0.1-1 mm.

The invention also provides a preparation method of the magnesium-based amorphous-calcium phosphate/calcium silicate composite filler, which is characterized by comprising the following steps:

(1) mixing the calcium phosphate/calcium silicate bone cement solid-phase powder with the magnesium-based amorphous powder/fiber to obtain solid-phase composite powder;

(2) preparing a buffer solution with the equal molar concentration of 0.2-1.0 mol% of sodium dihydrogen phosphate and disodium hydrogen phosphate by using analytically pure or analytically pure sodium dihydrogen phosphate, a disodium hydrogen phosphate reagent and deionized water or distilled water as a curing solution;

(3) and (3) preparing the solid-phase composite powder prepared in the step (1) and the curing liquid prepared in the step (2) according to the solid-liquid ratio of 0.1-3: 1 to prepare composite bone cement slurry, wherein the prepared bone cement slurry can be directly injected into a bone defect part by using an injector for use.

(4) And (4) injecting the bone cement slurry prepared in the step (3) into a mold for curing for 20 minutes to 6 hours, and then drying at 80 to 100 ℃ to prepare a blocky filling material for filling treatment of open bone defects.

The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler prepared by the method can be blended to form paste, and the injectable magnesium-based amorphous-calcium phosphate/calcium silicate bone cement with high bioactivity can be obtained and used for preparing injectable products for bone tissue wound repair.

The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler prepared by the method can be cured and dried in vitro after being blended to form paste to form a blocky filler for filling open bone defects.

The degradation speed of the calcium phosphate/calcium silicate bone cement is slow, the degradation speed of the magnesium-based amorphous powder/fiber is higher than that of the calcium phosphate/calcium silicate bone cement, magnesium ions with high biological activity generated by degradation can play a role of bone induction, the biological activity of the calcium phosphate/calcium silicate can be further enhanced, particularly in the initial stage of implantation, the calcium phosphate/calcium silicate can not play a role of biological activity due to the slow degradation speed, and the degradation speed of the magnesium-based amorphous powder/fiber is high, so that the bone induction can be effectively played in the initial stage, the early bone healing is promoted, and effective complementation is formed between the degradation speed of the magnesium-based amorphous powder/fiber and the time of the biological;

the vacancy left by the degradation of the magnesium-based amorphous powder/fiber and the hydrogen generated by the degradation can play a pore-forming role, bone cells can grow in the pores, the vascularization of the material is facilitated, and the supply of nutrition to the internal tissues of the material is ensured, so that the growth of new bone tissues and the reconstruction of autologous bones are promoted; meanwhile, the degradation of the magnesium-based amorphous powder/fiber can increase the contact surface area of calcium phosphate/calcium silicate and body fluid, and increase the degradation speed of the implant in the later period.

In addition, because the degradation speed of the magnesium-based amorphous alloy in vivo is lower than that of crystalline magnesium and the magnesium-based amorphous alloy, the problems of long solidification time and premature collapse in vivo of the composite material caused by high degradation speed of magnesium and the magnesium-based amorphous alloy can be avoided in the preparation process of the composite material.

The magnesium-based amorphous-calcium phosphate/calcium silicate composite filler product has the advantages of low cost of raw materials and simple preparation method, has high bioactivity, can form a porous structure in vivo, is beneficial to tissue repair, is mainly used for bone defect repair and bone tissue engineering scaffold materials, and can also be used as a dental repair material. When in use, the prepared slurry can be directly injected into the bone defect part by an injector, or the slurry can be injected into a mould to be solidified and molded and then implanted into the bone defect part.

Drawings

FIG. 1 is a photograph of MgZnCa Mg-based amorphous powder-calcium phosphate composite bone cement.

FIG. 2 shows that after MgZnCa Mg-based amorphous powder-calcium phosphate composite bone cement is cured and soaked in simulated body fluid for 24h, a large number of macroscopic pores appear on the surface.

FIG. 3 is calcium phosphate cement and Mg₆₉Zn₂₆Ca₅Macroscopic photographs of the magnesium-based amorphous powder-calcium phosphate composite bone cement before and at 7 and 14 days of immersion in simulated body fluid, wherein the ratio of calcium phosphate bone cement: before soaking (a), soaking for 7 days (b) and soaking for 14 days (c); mg (magnesium)₆₉Zn₂₆Ca₅Magnesium-based amorphous powder-calcium phosphate composite bone cement: d) before soaking, 7 days (e) and 14 days (f).

Detailed Description

The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.