Bioceramics

Bioceramics refers to a type of ceramic materials used for specific biological or physiological functions, that is, ceramic materials that are directly used in the human body or directly related to the human body, such as biology, medicine, and biochemistry. As a bioceramic material, it needs to have the following conditions: biocompatibility, mechanical compatibility, excellent affinity with biological tissues, anti-thrombotic, sterilization and good physical and chemical stability.

Bioceramic materials can be divided into biologically inert ceramics (such as Al2O3, ZrO2, etc.) and biologically active ceramics (such as dense hydroxyapatite, bioactive glass, etc.).

01— Biologically inert ceramics —

Bio-inert ceramics mainly refer to ceramic materials with stable chemical properties and good biological compatibility. Such as alumina, zirconia and medical carbon materials. The structure of this kind of ceramic materials is relatively stable, the bonding force in the molecule is strong, and they all have high strength, wear resistance and chemical stability.

Alumina bioceramics

The C-axis direction of single crystal alumina has quite high bending strength, good wear resistance, good heat resistance, and can be directly fixed with bone. It has been used as artificial bone, tooth root, joint and bolt. Moreover, the bolt does not rust, nor does it dissolve harmful ions. Unlike metal bolts, there is no need to take out the body. Because alumina ceramics are implanted into the human body to form a very thin fibrous membrane on the back surface, there is no chemical reaction at the interface, and it is mostly used in the restoration of the whole buttocks and the connection of the femur and the hip. The single crystal alumina manufactured by flame melting method has high strength, good wear resistance, and can be finely processed into artificial tooth roots, fracture fixers, etc. Polycrystalline alumina, namely corundum, has high strength and is used to make artificial hip joints, artificial bones, artificial tooth roots and joints. The mechanical properties of single crystal alumina ceramics are better than those of polycrystalline alumina, and they are suitable for parts with heavy load and high wear resistance requirements, but its disadvantage lies in the difficulty of processing. Chinese ceramics can fully meet the ISO standard in laboratory research level, but there is still a certain gap in clinical use, and the material does not meet the ISO standard.

Clinical application of single crystal alumina

Compared with alumina polycrystalline ceramics, it is used as an artificial joint handle with higher mechanical strength and is not easy to break. It can also be used as a fixing material for damaged bones, mainly used to make artificial bone screws, which have higher strength than artificial bone screws made of metal materials. It can be processed into various tooth roots with small size and high strength. Because the alumina single crystal has good affinity with human protein and strong binding force, it is beneficial to the adhesion of the gingival mucosa and the foreign tooth material.

Zirconia Bioceramics

Zirconia Ceramics (Zirconia Bioceramics) is a biologically inert ceramic with ZrO2 as the main component. Its distinctive feature is its high fracture toughness, high fracture strength and low elastic modulus. Zirconia (ZrO2) has extremely high chemical and thermal stability (Tm=2953K), is inert in the physiological environment, and has good biocompatibility. Pure zirconia has three allotropes, which can undergo crystal transformation (phase transformation) under certain conditions. When subjected to external force, the transition from t phase to m phase needs to absorb higher energy, relax the stress at the crack tip, increase crack propagation resistance and increase toughness, so it has very high fracture toughness.

Partially stabilized zirconia, like alumina, has good biocompatibility and high stability in the human body, and has higher fracture toughness and wear resistance than alumina. It is beneficial to reduce the size of implants and achieve low friction and wear. To manufacture tooth roots, bones, hip joints, composite ceramic artificial bones, valves, etc.

Biomedical applications: 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 withstand high shear stress. The wear rate of zirconia/zirconia paired grinding is 5000 times that of alumina/alumina paired grinding; but it shows good friction and wear performance when forming an oxide/UHMWPE friction pair.

Bioactive ceramics include surface bioactive ceramics and bioabsorbable ceramics, also called biodegradable ceramics. Bio-surface-active ceramics usually contain hydroxyl groups and can be made porous. Biological tissues can grow in and bond firmly to the surface; bio-absorbable ceramics are characterized by partial or full absorption, which can induce renewal in the organism Bone growth. Bioactive ceramics have osteoconductivity. They serve as a scaffold and bone formation takes place on its surface; it can also be used as a shell for various materials or filling bone defects. Bioactive ceramics include bioactive glass, hydroxyapatite ceramics, and tricalcium phosphate ceramics.

Bioactive glass and glass ceramics

(Bioactive Glass & Glass-ceramics)

The main component of biological glass ceramics is CaO-Na2O-SiO2-P2O5, which contains more calcium and phosphorus than ordinary window glass, and can naturally and firmly chemically bond with bone. It has unique properties that distinguish it from other biological materials. It can quickly cause a series of surface reactions at the implantation site, which ultimately leads to the formation of a carbonate-based apatite layer. Bioglass ceramics have good biocompatibility, the material is implanted in the body, there is no rejection, inflammation and tissue necrosis, and it can form osseous bonding with bone; it has strong bonding strength with bone, good interface bonding ability, and rapid osteogenesis . At present, this material has been used to repair ear ossicles and has a good effect on the restoration of hearing. However, due to its low strength, it can only be used on parts of the body that are not stressed.

The current method of preparing bioactive glass is mainly prepared by the sol-gel method. The material prepared by this method has a special chemical composition, nano-cluster structure and micropores, so it has a larger specific surface area and is more biologically active than other biological glasses. Glass-ceramic is better. Because the materials prepared by the sol-gel method have good purity, high uniformity, good biological activity and large specific surface area, they have better research and application value, especially the use of bioactive glass porous materials as scaffolds for bone tissue engineering Has a very good prospect.

The most significant feature of bioactive glass and glass ceramics is that after implantation in the human body, the surface condition changes dynamically with time, and a bioactive hydroxyapatite (HCA) layer is formed on the surface, which provides a bonding interface for the tissue.

A. Composition: The composition of bioactive glass is mainly: SiO2, Na2O, CaO, P2O5, etc. Bioactive glass ceramics are polycrystals obtained by controlling crystallization on the basis of bioactive glass. Compared with traditional soda-lime-silica glass, it has three major composition characteristics: low SiO2 content; high Na2O and CaO content; high CaO/P2O5 ratio.

B. Properties: fast surface reaction; amorphous two-dimensional structure makes strength and fracture toughness low; elastic modulus (30-35MPa) is low, close to cortical bone; machinable bioglass has good processing performance.

C. Preparation process: The preparation process of bioactive glass is basically the same as the traditional glass preparation process, including weighing, mixing, fusion, melting, homogenization, glass formation, etc. Glass ceramics also need to control glass nucleation and grain growth under a certain heat treatment system.

D. Clinical application:

a) 45S5 bioactive glass is used for middle ear ossicle replacement, jaw defect repair, periodontal defect repair, bone crest maintenance implants, and does not cause cell damage, degradation products, and infection.

b) Ceravital bioactive glass ceramic is used in middle ear surgery. It is a low sodium and potassium bioactive glass ceramic.

c) Apatite-wollastonite active glass-A-WGC, used for spinal prosthesis, chest and frontal bone repair and bone defect repair, has been successfully applied to tens of thousands of patients.

d) Machinable bioactive glass-MBGC], mainly used in maxillofacial, spine, alveolar hard tissue repair and oral repair, which is characterized by excellent workability and osseointegration.

Calcium phosphate bioactive ceramics

Calcium phosphate ceramics (CPC) is an important type of bioactive ceramic materials. At present, the most researched and applied ones are hydroxyapatite (HA) and tricalcium phosphate (TCP). Calcium phosphate ceramic contains two components: CaO and P2O5, which are important inorganic substances that constitute the hard tissues of the human body. After being implanted in the human body, the surface of the ceramics can be bonded to the human body tissues to achieve complete affinity. Among them, HA is very similar to human bones and teeth in composition and structure, has high mechanical properties, and has low solubility in the physiological environment of the human body; TCP has good binding properties to bones, and has no rejection reaction. The degree of dissolution is much higher than that of HA, which can be slowly degraded and absorbed by body fluids, providing abundant calcium and phosphorus for the growth of new bones, and promoting the growth of new bones. In addition to these two, calcium phosphate bioceramics also include degradable and absorbing zinc-calcium-phosphorus oxide ceramics (ZCAP), zinc sulfate-calcium phosphate ceramics (ZSCAP), aluminum calcium phosphate ceramics (ALCAP) and iron-calcium- Phosphorus oxide ceramics (FECAP), etc.

A. Overview of composition and physical and chemical properties

The classification of calcium phosphate compounds is usually carried out according to the atomic ratio of Ca/P (calcium to phosphorus ratio). Calcium phosphate ceramics are a general term for calcium phosphate ceramics with different calcium to phosphorus ratios.

Various calcium phosphate compounds have a certain degree of solubility. The solubility products of calcium hydrogen phosphate, tricalcium phosphate and hydroxyapatite are as follows: The structure of various calcium phosphate compounds at high temperatures and their calcium-phosphorus ratio, temperature, heating rate, and atmosphere Other factors are related; the different synthesis process will also affect its thermal characteristics (mainly its thermal stability).

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, bone repair materials made of dicalcium phosphate and tricalcium phosphate can gradually dissolve, and at the same time precipitate crystals into hydroxyapatite.

B. Hydroxyapatite ceramics

The composition of hydroxyapatite (HA or HAP) is similar to that of natural apatite minerals. It is the main inorganic component of vertebrate bones and teeth. The structure is also very similar, showing a flaky microcrystalline state. It is used as a bone substitute for bone transplantation. HA has good biocompatibility and is not only safe and non-toxic when implanted in the body, it can also conduct bone growth.

HA can attach bone cells to its surface. With the growth of new bone, this connection zone gradually shrinks, and HA becomes a part of the bone through the outer layer of the lens. The new bone can be grafted along the junction between the HA implant and the original bone. The penetrating pores on the surface or inside the body cling and grow. HA bioactive ceramics are typical bioactive ceramics, which can form a chemical bond with tissues on the interface after being implanted in the body. The bonding mechanism between HA bioactive ceramics and bone is not like that of bioglass, which requires the formation of a silicon-rich layer on its surface and the formation of an intermediate bonding band to achieve bonding. After the dense hydroxyapatite ceramics are implanted in the bone, the osteoblasts directly differentiate on the surface to form a bone matrix, producing an amorphous electron density band with a width of 3~5 μm. The collagen fiber bundles grow into this area and between the cells. In the meantime, bone salt crystallization occurs in this amorphous zone. As the mineralization matures, the amorphous band shrinks to 0.05~0.2μm, and the bonding between the hydroxyapatite implant and the bone is achieved through this very narrow bonding band.

After the artificial joint treated with HA surface coating is implanted in the body, the surrounding bone tissue can quickly directly deposit on the surface of hydroxyapatite, and form chemical bonds with the calcium and phosphorus ions of hydroxyapatite, and the bond is tight, and there is no fiber membrane in the middle. . HA bioceramics are implanted into soft tissues such as muscles or ligaments or are tightly surrounded by a thin layer of connective tissue, without inflammatory cells and microcapillaries. When used for transdermal planting, it can be closely attached to the neck and epithelial tissues without inflammation and infection. Therefore, HA bioactive ceramics are also suitable for transdermal devices and soft tissue repair.

The preparation of HA ceramics can generally be obtained from the decomposition of animal bone tissue and artificial synthesis. The latter is divided into wet method and solid phase reaction. The most commonly used method is the reactive co-precipitation method, which is to prepare calcium raw materials and phosphate or phosphoric acid respectively into liquids of appropriate concentration, according to the atomic ratio of calcium to phosphorus 1.67, and under pH>7 environment, control the appropriate temperature to react Synthesis, the precipitate is dehydrated, dried, and calcined at a high temperature to obtain a light green synthetic crystal agglomerate with a purity of over 99.5%, and its chemical composition is mainly CaO, P2O5.

A single HA has poor forming and sintering properties, and is easy to deform and crack. Adding ZrO2+ Y2O3, ZnO and CPM compound reagent containing magnesium salt, etc., 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 as a repair and replacement material for biological hard tissues, such as oral implants, alveolar ridge heightening, periodontal pocket filling, frontal bone defect repair, ear ossicle replacement, etc. Because the mechanical strength is not high enough, it can only be used in the above parts that do not bear heavy load. Due to the excellent strength and toughness of natural bone, people thought of improving the performance of bioceramics to repair bone repair materials through a bionic approach. The bone microstructure model proposed by Landis et al. has been widely cited, although there are still some details that have not been experimentally verified.

Among calcium phosphate compounds, apatite is the most studied, and its general chemical formula is: M10(XO4)6Z2. M-is a divalent metal ion, XO4-is a pentavalent anion, and Z-is a monovalent anion. The hydroxyapatite ceramics will be discussed in detail below.

C. Performance application of hydroxyapatite ceramics

The structure of synthetic hydroxyapatite is similar to biological bone tissue, so synthetic hydroxyapatite has the same properties as biological hard tissue. For example, Ca: P≈1.67, density≈3.14, mechanical strength greater than 10MPa, non-toxic to organisms, non-irritating, biologically compatible, not absorbed, and can induce new growth.

At home and abroad, hydroxyapatite has been used for alveolar, bone defect, brain surgery repair, filling, etc., for the manufacture of ear-ossicular chain and plastic surgery materials. In addition, it can also be made into artificial bone nucleus to treat bone tuberculosis.

Tricalcium Phosphate

The widely used biodegradable ceramic β-tricalcium phosphate (β-TCP for short) is a trigonal crystal system with a calcium-phosphorus atomic ratio of 1.5, which is a high-temperature phase of calcium phosphate. The biggest advantage of β-TCP is that it has good biocompatibility, and it fuses directly with bone after implantation in the body, without any local inflammatory reaction and systemic side effects.

The calcium to phosphorus ratio plays an important role in determining the solubility and absorption tendency in the body, so TCP is easier to dissolve in the body than HA, and its solubility is about 10-20 times higher than that of HA. The commonly used β-TCP can be gradually degraded when implanted in the body, and the degradation rate may vary due to its surface structure, crystal configuration, porosity and implanted animals, and its strength often decreases with degradation. It has been proved that changing the pore size and the purity of the material can slow down the degradation rate and increase the biological strength.

Compared with other ceramics, β-TCP ceramics are more similar to the nature and structure of human bones and natural teeth. In the living body, the dissolution of hydroxyapatite is harmless, and it relies on supplementing calcium and phosphate ions from body fluids to form new Bone can produce reactions such as decomposition, absorption and precipitation at the joint interface of bones to achieve a firm bond.

The disadvantage of β-TCP ceramics is that it has low mechanical strength and cannot withstand strong impacts. Mixing β-TCP with other materials to make dual-phase or multi-phase ceramics is one of the ways to improve its mechanical strength. It is generally believed that the bone conduction effect of biphasic calcium phosphate (BCP) is better than that of a single HA or TCP. It can combine the high strength of HA and the good biodegradability of TCP, and the chemical composition is similar to bone. Bruder et al. inoculated bone marrow stroma cells (BMS) on porous BCP, and succeeded in repairing a 21mm long canine femoral segmental defect. Fu Rong et al. found that culturing BMS on BCP can better express the characteristics of osteoblasts, indicating that BCP is more suitable for matrix materials for bone tissue engineering.

With the progress of society, human beings are no longer satisfied with simply imitating the shapes of human organs, but are pursuing new materials with perfect functions. Bioceramics has become an indispensable and important part of today's medical field. At present, the material science community has done a lot of research in this area. With the rapid development of modern science and continuous improvement in technology, the preparation methods of bioceramics are becoming more and more feasible.

A variety of Ca-P ceramics and organic materials are used as scaffold materials for bone tissue engineering in clinical trials, such as TCP + collagen, nanocrystalline HA + collagen, TCP + platelet rich plasma, etc. There are two types of shape memory alloys: self-expandable and balloon-expandable. Mainly used for advanced malignant tumors caused by narrow biliary tract, ideal biomedical materials should be non-toxic, non-sensitizing, non-irritating, non-genotoxic and non-carcinogenic to humans. Therefore, it is very important to understand the biological response of biomedical materials to the human body. These reactions mainly include tissue reaction, blood reaction and immune reaction.

Through continuous research and development, more excellent properties of bioceramics will be developed and applied. In short, bioceramics has a lot of research space and broad development prospects.