Bioinert ceramics
Bioinert ceramics mainly refer to ceramic materials with stable chemical properties and good biocompatibility. Such as alumina, zirconia and medical carbon materials. These ceramic materials have relatively stable structure, strong intermolecular binding force, high strength, wear resistance and good chemical stability.
1. alumina bioceramics
Single crystal alumina has high bending strength in the direction of C axis, good wear resistance and heat resistance, and can be directly fixed with bone. It has been used as artificial bone, root, joint and bolt. Moreover, the bolt will not rust and will not dissolve harmful ions. Unlike metal bolts, it does not need to be taken out of the body. In the late 1960s, it was widely used in hard tissue repair. From the 1970s to the mid-1980s, many countries in the world, such as the United States, Japan, Switzerland and other countries, conducted extensive research and application on oxide ceramics, especially alumina bioceramics. Because alumina ceramics are implanted into human body to form a very thin fibrous membrane, there is no chemical reaction at the interface, which is mostly used for total hip reduction and repair and the connection between femur and hip joint. Single crystal alumina produced by flame melting method has high strength and good wear resistance, and can be finely processed to make artificial roots and fracture fixators. Polycrystalline alumina, namely corundum, has high strength and is used to make artificial hip joints, artificial bones, artificial roots and joints. The mechanical properties of single crystal alumina ceramics are better than polycrystalline alumina, which is suitable for parts with high load and high wear resistance, but its disadvantage is that it is difficult to process. China ceramics can meet the ISO standard in laboratory research, but there is still a gap in clinical application, and the materials do not meet the ISO standard.
International Organization for Standardization (ISO) requirements for medical alumina implants. Physical properties of alumina ceramics
6474 zirconia ceramic compact bone cancellous bone mass fraction/%alumina >: 99.8 alumina >; 99.5 zirconia >; 97 density/(g cm-3) > 3.93 >: 3.90 6.05 1.6-2. 1 average particle size/mm-3 3-6; 2000 1300 compressive strength/mpa45002000100-2302-12 flexural strength/mpa595 > 4001000 50-150 young's modulus/gpa4000.
First, the pulling method
That is, the raw materials are put into a crucible, the crucible is put into a single crystal furnace, the raw materials are completely melted by heating, the seed crystal mounted on the seed crystal rod is immersed in the melt to contact with the liquid surface, the temperature is precisely controlled and adjusted, the seed crystal rod is slowly pulled upward and rotated at a certain speed, so that the crystallization process is continuously carried out on the solid-liquid interface until the crystal growth reaches a predetermined length. The speed of pulling the seed crystal rod is 1.0-4 mm/min, the rotation speed of the crucible is 10 rpm, and the rotation speed of the seed crystal rod is 25 rpm.
B, guide mode method
Referred to as EFG method, in the melt of the single crystal material to be grown, a hollow mold with the same cross-sectional shape as the crystal to be grown is taken as the guide mold under the top caving surface, and the material used in the mold should be able to fully wet the melt without reaction. Due to capillary phenomenon, the melt rises to the top surface of the die, forming a thin melt surface. When the seed crystal is immersed in the matrix, the crystal with the same cross section as the top of the mold can be pulled out.
C, vapor phase chemical deposition growth method
Vaporize metal hydroxide, halide or metal organic matter into gas phase, or use appropriate gas as carrier, transport it to a low temperature area for condensation, and deposit it on a certain substrate through chemical reaction to form thin film crystals.
D, flame melting method
The raw materials are put into a hopper, dropped through an inverted oxyhydrogen flame nozzle, melted and deposited on a refractory support column in a holding furnace to form a molten layer, and crystallized while falling on the support column. This method has the advantages of fast crystal growth, simple process and no need of expensive iridium crucible and container, so it is more economical.
Clinical application of single crystal alumina.
Compared with alumina polycrystalline ceramics, it has higher mechanical strength and is not easy to break. It can also be used as a fixation material for injured bones, mainly used to make artificial bone screws, which is stronger than metal materials. It can be processed into various teeth with small size and high strength. Because alumina single crystal has good affinity and strong binding force with human protein, it is beneficial to the adhesion of gingival mucosa and heterodentate materials.
2. Zirconia ceramics
Zirconia bioceramics are biologically inert ceramics with zirconia as the main component, which have the characteristics of high fracture toughness, high fracture strength and low elastic modulus. Zirconia (ZrO2 _ 2) has high chemical stability and thermal stability (Tm=2953K), is inert in physiological environment and has good biocompatibility. There are three allotropes in pure zirconia, which can undergo crystal transformation (phase transformation) under certain conditions. Under the action of external force, the transformation process from T phase to M phase needs to absorb high energy, relax the stress at the crack tip and increase the crack diffusion resistance to toughen it, so it has very high fracture toughness.
Partially stabilized zirconia, like alumina, has good biocompatibility, high stability in human body, higher fracture toughness and wear resistance than alumina, which is conducive to reducing the size of implants and achieving low friction and wear. It can be used to manufacture tooth roots, bones, femoral joints, composite ceramic artificial bones, valves, etc. Scientists in Shanghai have also successfully developed plasma sprayed zirconia coating materials for artificial joints and won the National Invention Award.
(Performance comparison of alumina and zirconia ceramics for surgical implantation) Density of alumina and zirconia (g/cm) 3.98 6.05 particle size (mm) 3.6 0.2-0.4 flexural strength (MPa) 595 1000 compressive strength (MPa) 4200 2000 Young's modulus (GPa). Preparation technology of 400 150 hardness (HV) 2400 1200 fracture toughness KIC(MN/m) 5 7 zirconia ceramics: Zirconium SiO _ 4 is rich in natural resources, and pure zirconia powder can be prepared by chemical method, and zirconia ceramics can be obtained after adding flux and appropriate modifier auxiliary materials, molding and sintering.
Biomedical application: Based on the excellent biocompatibility, good fracture toughness, high fracture strength and low elastic modulus of zirconia ceramics, it is suitable for making artificial joints that need to bear high shear stress. The wear rate of zirconia/zirconia is 5000 times that of alumina/alumina. However, after the oxidation /UHMWPE friction pair is formed, it shows good friction and wear performance.
3. Carbon biomaterials
Carbon is widely distributed in nature, with elemental carbon, but more in the form of compounds. There are many allotropes of elemental carbon, mainly including diamond structure, graphite structure and amorphous structure. Carbon is a biologically inert material with good chemical stability, non-toxicity, good affinity with human tissues and no rejection reaction in human body. Especially amorphous carbon has excellent mechanical properties, and its properties can be changed by adjusting its composition and structure to meet different application requirements. Although amorphous carbon does not form a chemical bond with human tissues, it can make human soft tissues grow into the gaps of carbon to form a firm bond, and the human soft tissues around carbon can regenerate rapidly. Some people think that amorphous carbon can induce tissue growth. Because of its unique surface composition and structure, amorphous carbon is widely used as cardiovascular materials because of its very small coagulation caused by long-term contact with blood and no thrombosis.
Amorphous carbon commonly used in medicine includes: low temperature isotropic carbon, glassy carbon, ultra-low temperature isotropic carbon, diamond-like carbon and carbon fiber reinforced composite carbon materials.
A. Low temperature isotropic pyrolytic carbon (LTIC), glassy carbon (glassy carbon) and ultra-low temperature isotropic carbon (ULTIC) are all disordered lattices, collectively referred to as turbine layer carbon. The microstructure of disordered carbon is disordered and looks very complicated, but it is actually similar to graphite structure. From the point of view of biomedical materials, the biggest feature of turbine layer carbon is its excellent cell biocompatibility and anticoagulation, especially LTIC and ULTIC.
The carbon density (g/cm) of LTI carbon polycrystalline graphite glass carbon ULTI is1.5-1.81.7-2.21.4-1.6/kloc. 15-250 3-51-48-15 expansion coefficient (10/k)0.5-5.05-62-6- Vickers hardness (DPH). 50-120 230-370150-200150-250 Young's modulus (GPA) 4-1227-3/kloc-0. 65-300 350-530 69-206 345-690 Fracture deformation (%) 0.1-0.71.5-2.00 0.8-1.32.0-5.0b, glassy carbon. Glassy carbon is a kind of non-graphitizable monolithic carbon with high isotropic characteristics. The primary surface and cross section have the appearance characteristics of glass body, but only the appearance, without the spatial network structure of silicate glass. Glassy carbon is composed of irregular particles of about 5 nanometers, with very low porosity and low permeability to liquids and gases.
C. diamond-like carbon. Diamond-like carbon (DLC) contains a small amount of diamond microcrystals and graphite microcrystals besides amorphous carbon, and its physical properties are very similar to diamond. Because the raw materials for preparing diamond-like carbon are hydrocarbons, there are many hydrocarbon groups in diamond-like carbon besides carbon. The properties of diamond-like carbon also change greatly with the types and quantities of hydrocarbon groups. It has excellent characteristics such as high hardness (HV (kg/mm2)1200-1800), high wear resistance, low friction coefficient, high corrosion resistance, histocompatibility and blood compatibility. Its preparation process includes: plasma chemical vapor deposition, ion beam enhanced deposition, ion plating and PIII-IBED.
(Application of medical carbon materials) ULTI blood channel device LTI/ULTI pacemaker electrode porous glass -ULTI oxygen microporous separation membrane coating ULTI ear canal LTI root coating, tooth implant coating ULTI, DLC artificial joint coating LTI, DLC percutaneous connector coating LTI bioactive ceramics are needed.
Bioactive ceramics include surface bioactive ceramics and bioabsorbable ceramics, also known as biodegradable ceramics. Biosurfactant ceramics usually contain hydroxyl groups, and can also be made porous, so that biological tissues can grow on its surface and firmly combine; Bioabsorbable ceramics are characterized by partial or total absorption, which can induce the growth of new bones in organisms. Bioactive ceramics have bone conductivity. As a scaffold, osteogenesis is carried out on its surface. It can also be used as a shell for various substances or to fill bone defects. Bioactive ceramics include bioactive glass, hydroxyapatite ceramics and tricalcium phosphate ceramics.
1. bioactive glass and glass ceramics (bioactive glass &; Glass ceramics)
The main component of bioglass ceramics is CaO-Na2O-S iO2-P2O5, which contains more calcium and phosphorus than ordinary window glass, and can naturally and firmly chemically combine with bones. It has unique properties different from other biomaterials, and can produce a series of surface reactions at the implantation site quickly, which eventually leads to the formation of carbonate-based apatite layer. Bio-glass ceramics have good biocompatibility, and the materials implanted in the body have no rejection, inflammation and tissue necrosis, and can form bone integration with bone; High bonding strength with bone, good interface bonding ability and fast osteogenesis. At present, this material has been used to repair the ossicle, which has a good effect on restoring hearing. However, due to its low strength, it can only be used in parts of the human body with little stress. At present, the main method to prepare bioactive glass is sol-gel method. The material prepared by this method has special chemical composition, nano-cluster structure and micropores, large specific surface area and better biological activity than other bioglass and glass-ceramics. The materials prepared by sol-gel method have good purity, high uniformity, good bioactivity and large specific surface area, so they have good research and application value, especially bioactive glass porous materials have good prospects in bone tissue engineering scaffolds.
The most remarkable feature of bioactive glass and glass-ceramics is that the surface state changes dynamically with time after being implanted into human body, and a layer of bioactive hydroxyapatite (HCA) is formed on the surface, which provides a bonding interface for tissues.
A composition: bioactive glass is mainly composed of silicon dioxide, sodium oxide, calcium oxide and phosphorus pentoxide. Bioactive glass-ceramics are polycrystals obtained by controlling crystallization on the basis of bioactive glass. Compared with the traditional soda-lime-silica glass, it has three characteristics: low silica content; The content of Na2O and CaO is high; CaO/P2O5 ratio is high.
B, properties: rapid surface reaction; The amorphous two-dimensional structure makes the strength and fracture toughness lower; The elastic modulus (30-35MPa) is low, close to cortical bone. Machinable bioglass has good processability.
C preparation process: the preparation process of bioactive glass is basically the same as the traditional glass preparation process, including weighing, mixing, melting, melting, homogenization, glass forming and so on. Glass ceramics also need to control glass nucleation and grain growth under a certain heat treatment system.
D, clinical application: a) 45S5 bioactive glass can be used for middle ear small bone replacement, jaw defect repair, periodontal defect repair and bone ridge maintenance implants, and will not cause cell damage, degradation products and infection. B) Ceravital bioactive glass ceramic is used in middle ear surgery, which is a kind of bioactive glass ceramic with low sodium and potassium. C) apatite-wollastonite active glass -A-WGC has been used in spinal prosthesis, chest and forehead bone repair and bone defect repair, and has been successfully applied to tens of thousands of patients. D) Machinable bioactive glass -MBGC], which is mainly used for hard tissue repair of maxillofacial region, spine and alveolar cavity and oral cavity repair, is characterized by excellent machinability and osseointegration.
2. Calcium phosphate bioactive ceramics
Calcium phosphate ceramic is an important bioactive ceramic. At present, hydroxyapatite and tricalcium phosphate are the most widely studied and applied. Calcium phosphate ceramics contain two components, CaO and P2O5, which are important inorganic substances that constitute human hard tissues. After being implanted into human body, its surface can be combined with human tissue through bonds to achieve complete affinity. Among them, HA is very similar to human bones and teeth in composition and structure, with high mechanical properties and low solubility in human physiological environment. TCP has a good combination with bone, no rejection, and its solubility in aqueous solution is much higher than that of HA. It can be slowly degraded and absorbed by body fluids, providing rich calcium and phosphorus for new bone growth and promoting new bone growth. In addition to these two kinds, calcium phosphate bioceramics include degradable and absorbable zinc-calcium-phosphorus oxide ceramics (ZCAP), zinc sulfate-calcium phosphate ceramics (ZCAP), aluminum-calcium phosphate ceramics (ALCAP) and iron-calcium-phosphorus oxide ceramics (FECAP).
A. Overview of composition and physicochemical properties
The classification of calcium phosphate compounds is usually based on the atomic ratio of Ca/P (calcium-phosphorus ratio), and calcium phosphate ceramics are the general name of calcium phosphate ceramics with different calcium-phosphorus ratios.
(Calcium phosphate is classified by Ca/P) The molecular formula of calcium-phosphorus ratio is abbreviated as 2.0 Ca4O(PO4)2 tetracalcium phosphate TTCP1.67ca10 (PO4) 6 (OH) 2 hydroxyapatite HA.
All kinds of calcium phosphate compounds have certain solubility. The solubility products of dicalcium phosphate, tricalcium phosphate and hydroxyapatite are as follows:
Calcium hydrogen phosphate pK=6.57
Tricalcium phosphate pK=28.7
Hydroxyapatite pK=57.8
Calcium hydrogen phosphate has the strongest solubility in water, followed by tricalcium phosphate and hydroxyapatite is the most stable. Therefore, the bone repair materials made of calcium hydrogen phosphate and tricalcium phosphate can gradually dissolve and precipitate into hydroxyapatite.
Hydroxyapatite ceramics
Hydroxyapatite (HA or HAP for short) is similar to natural apatite in mineral composition, and is the main inorganic component of vertebrate bones and teeth, and its structure is also very similar, showing a flaky microcrystalline state. As a bone substitute for bone transplantation. HA has good biocompatibility, which is not only safe and non-toxic, but also can guide bone growth. HA can attach bone cells to its surface. With the growth of new bone, this connecting zone gradually shrinks, and HA becomes a part of bone through the outer layer of the crystal. New bone can climb and grow from the joint of HA implant and original bone along the through hole on the surface or inside of the implant. HA bioactive ceramics are typical bioactive ceramics, which can form chemical bonds with tissues at the interface after implantation. Different from bioglass, the bonding mechanism between HA bioactive ceramics and bone does not need to form a silicon-rich layer on its surface, and then form an intermediate bonding zone to achieve bonding. After the dense hydroxyapatite ceramics are implanted into bone, osteoblasts directly differentiate on its surface to form a bone matrix, resulting in an amorphous electron density band with a width of 3~ 5 microns. Collagen fiber bundles grow between this region and the cells, and bone salt crystallization occurs in this amorphous band. With the maturity of mineralization, the amorphous zone shrinks to 0.05~ 0.2μm, and the combination of hydroxyapatite implant and bone is realized through this narrow combination zone.
After the artificial joint treated by HA surface coating is implanted into the body, the surrounding bone tissue can be directly and rapidly deposited on the surface of hydroxyapatite, and form chemical bonds with calcium and phosphorus ions of hydroxyapatite, which are closely combined without fibrous membrane in the middle. HA bioceramics are implanted in soft tissues such as muscles or ligaments or closely surrounded by a thin layer of connective tissue, without inflammatory cells and capillaries. When it is implanted through the skin, it can approach the epithelial tissue of the neck without inflammation and infection. Therefore, HA bioactive ceramics are also suitable for percutaneous devices and soft tissue repair.
The preparation of HA ceramics can generally be obtained by decomposing animal bone tissue and artificial synthesis, and the latter can be divided into wet method and solid state reaction. The most commonly used method is reactive precipitation, that is, calcium raw materials and phosphate or phosphoric acid are prepared into liquids with appropriate concentrations respectively, and mixed at pH > > according to the atomic ratio of calcium to phosphorus 1.67. 7. Dehydrate and dry the precipitate, and then calcine it at high temperature to obtain light green synthetic crystal aggregate with purity above 99.5%, and its chemical components are mainly CaO and P2O5. Single HA has poor sintering performance and is easy to deform and crack. Adding ZrO _ 2+Y _ 2O _ 3, ZnO and CPM compound reagent containing magnesium salt can make it have good biocompatibility and sufficient mechanical strength, and it is non-toxic. Continuous hot isostatic pressing sintering is an effective method to prepare high-density HA with theoretical density. This material is mainly used to repair and replace biological hard tissues, such as oral implantation, alveolar ridge elevation, periodontal pocket filling, frontal bone defect repair, ear small bone replacement and so on. Because the mechanical strength is not high enough, it is only used in the above-mentioned parts that do not bear heavy load. Because natural bone has excellent strength and toughness, people think of bionic methods to improve the performance of bioceramic bone repair materials. The bone microstructure model proposed by Landis et al. has been widely cited, although some details have not been verified by experiments.
Among calcium phosphate compounds, apatite is the most studied, and its chemical general formula is: M 10(XO4)6Z2. M- is a divalent metal ion, XO4- is a pentavalent anion, and Z- is a monovalent anion. Hydroxyapatite ceramics will be discussed in detail below.
Manufacturing technology of hydroxyapatite ceramics;
First, the solid-state reaction method
This method is basically the same as ordinary ceramics. Grinding and mixing the raw materials according to the formula, and synthesizing at high temperature.
1000- 1300℃
6 CAH po 4·2H2O+4 CaCO 3·ca 10(PO4)6(OH)2+4 CO2+4H2O
B, hydrothermal reaction method
CaHPO4 and CaCO3 were mixed according to the molar ratio of 6∶4, and then wet ball milling was carried out for 24 hours. Pour the ball-milled slurry into a container, add enough distilled water, stir at a constant temperature of 80- 100℃, and after the reaction is completed, place it for precipitation to obtain white hydroxyapatite precipitation. The reaction formula is as follows:
6cahpo4+4caco3═ca 10(po4)6(oh)2+4co2+2h2o
C, precipitation reaction method
In this method, Ca(NO3)2 reacts with (NH4)2HPO4 to obtain white hydroxyapatite precipitate. The reaction is as follows:
10Ca(NO3)2+6(NH4)2 hpo 4+8 NH3·H2O+H2O = ca 10(PO4)6(OH)2+20nh 4 no 3+7H2O
In addition, there are other methods to prepare hydroxyapatite.
Properties and application of hydroxyapatite ceramics
The structure of synthetic hydroxyapatite is similar to biological bone tissue, so synthetic hydroxyapatite has the same performance as biological hard tissue. For example, Ca: P ≈ 1.67, density ≈3. 14, mechanical strength greater than 10MPa, non-toxic, non-irritating, good biocompatibility, non-absorption, and can induce new growth.
At home and abroad, hydroxyapatite has been used to repair and fill alveolar bone defects and brain surgery. , has been used to make otoauditory bone chains and plastic surgery materials. In addition, it can also be made into artificial bone nucleus for the treatment of bone tuberculosis.
3. Tricalcium phosphate
At present, the widely used biodegradable ceramic β-tricalcium phosphate (β-TCP) belongs to ternary system, and the atomic ratio of calcium to phosphorus is 1.5, which is the high temperature phase of calcium phosphate. The biggest advantage of β-TCP is its good biocompatibility, which can be directly fused with bone after being implanted in the body, without any local inflammatory reaction and systemic toxic side effects.
The ratio of calcium to phosphorus plays an important role in determining the solubility and absorption trend in vivo, so TCP is easier to dissolve in vivo than HA, and its solubility is about 10~ 20 times higher than HA. The commonly used β-TCP can be gradually degraded when implanted into the body, and the degradation rate can vary with its surface structure, crystal configuration, porosity and implanted animals, and its strength often weakens with degradation. It has been proved that changing pore size and material purity can slow down the degradation rate and improve the biological strength.
Compared with other ceramics, β-TCP ceramics are more similar to human bones and natural teeth in nature and structure. In living organisms, the dissolution of hydroxyapatite is harmless. By supplementing calcium and phosphorus ions from body fluids to form new bones, reactions such as decomposition, absorption and precipitation occur at the bone-joint interface, so as to achieve a firm combination.
The disadvantage of β-TCP ceramics is that it has low mechanical strength and cannot withstand the impact of force. Mixing β-TCP with other materials to make biphasic or multiphase ceramics is one of the ways to improve its mechanical strength. Generally speaking, biphasic calcium phosphate (BCP) has better bone conduction effect than single HA or TCP, and can combine the advantages of high strength of HA and good biodegradability of TCP, and its chemical composition is similar to that of bone. Bruder et al. successfully inoculated bone marrow stromal cells (BMS) onto porous BCP to repair the segmental defect of dog femur with a length of 265438±0mm ... Fu Rong et al. found that BMS cultured on BCP can better express the characteristics of osteoblasts, indicating that BCP is more suitable as a matrix material for bone tissue engineering.