Basic introduction Chinese name: Biological Materials MBTH: Biological Materials Time: 1990s Features: Broad development prospects Disciplines: biological development, introduction, principle, related products, performance, functionality, compatibility, compatibility reaction, host reaction, material reaction, classification characteristics, classification, characteristics, application development, performance requirements, material classification, Performance evaluation, mechanical properties, evaluation criteria, human influence, terminology, definition, material science and development Since the late 1990s, biomaterial science technology has developed rapidly all over the world. Even in today's global economic downturn, biomaterials still maintain a high growth rate of 13% every year, which fully reflects its strong vitality and broad development prospects. Modern medicine is developing in the direction of regeneration and reconstruction of damaged tissues and organs, recovery and improvement of human physiological functions, personalized and minimally invasive treatment. Traditional inanimate medical materials such as metals, polymers and bioceramics can no longer meet the requirements of medical development, and biomedical materials science and engineering are facing new opportunities and challenges. In the future, the market share of biomedical materials is likely to catch up with drugs. Therefore, it is urgent to strengthen the clinical application research and popularization of biomedical materials, and focus on developing the integrated system of R&D, production and marketing of biomedical materials in China. In fact, China has made a great breakthrough in basic research in biomaterial science and is one of the advanced countries in the world. However, the level of industrialization still needs to be improved, and the industrial scale is small and the development is relatively backward, which can not meet the actual needs of universal medical care. With the strong support of national policies and economy, the industrialization of biomaterials in China will be accelerated. Enterprises should enhance their independent innovation ability, further solve the situation of dependence on imports, and at the same time increase their export efforts to achieve leap-forward development and expand the international influence of China's biomaterial products. Biomaterials are also called biotechnology or biotechnology. Applying the principles of biology and engineering, aiming at the unique functions of biomaterials and organisms, the comprehensive science and technology of new biological varieties with specific characteristics are established directionally. Bioengineering was developed on the basis of molecular biology and cell biology in the early 1970s, including genetic engineering, cell engineering, enzyme engineering and fermentation engineering. They are interrelated, among which genetic engineering is the foundation. Only by transforming organisms through genetic engineering can we produce more and better biological products according to human wishes. The results of genetic engineering can only be transformed into products through projects such as fermentation. Related products bioengineering can produce a large number of cheap drugs to prevent and treat human diseases, such as insulin, interferon, growth hormone, hepatitis B vaccine and so on. Bioengineering is also widely used in food and light industry. During the period of 1983, the annual output of high fructose syrup used to make drinks in the United States reached 6 million tons, thus reducing the consumption of sucrose by half. The application of bioengineering technology has greatly changed the breeding work, such as transferring disease-resistant genes into tobacco, cultivating new tobacco varieties and preventing pests; Some achievements have also been made by transferring the nitrogen-fixing genes of rhizobia from lower organisms into the cells of higher crops, so that they can produce nitrogen fertilizer by themselves. All countries in the world attach great importance to bioengineering, and China also lists bioengineering as one of the key scientific research projects. The research of bioengineering will have a great impact on human production and lifestyle. Performance functionality refers to a series of properties that biomaterials should have when they have or complete a certain biological function. According to the purpose, it is mainly divided into: * the function of bearing or transmitting load. Such as artificial bones, joints and teeth, play a leading role in controlling the flow of blood or body fluids. Such as artificial valves and blood vessels. Such as pacemaker, intraocular lens, cochlea, etc. Compatibility, such as fillers used in cosmetic surgery, refers to the ability of biomaterials to function effectively in vivo or on the body surface for a long time. It is used to characterize the biological behavior of biological materials interacting with organisms in vivo. According to the contact position between materials and organisms, it is divided into: * blood compatibility. This material is used in the contact between cardiovascular system and [[blood]], mainly to investigate the interaction with blood * and the contact with tissues and organs outside the cardiovascular system. This paper mainly investigates the interaction with tissues, also known as general biocompatibility * mechanical compatibility. Investigating the consistency between mechanical properties and organisms Biomaterials and Nanobiotechnology is an international, interdisciplinary and original English document published by American Research Press on the preparation, properties and evaluation of biomaterials. Nano-materials cover physical, chemical, toxicological, electrochemical, mechanical and optical characteristics, as well as the application of biotechnology (pharmacy, drug delivery system, cosmetics, food technology, biotransformation, renewable energy and energy storage, biosensing, nano-drugs, tissue engineering, implantable medical devices, biophotonics, nano-photodynamic therapy, oncology). Compatibility reaction host reaction (1) biological reaction a: blood reaction 1 platelet thrombosis; 2. Activation of coagulation system; 3. Activation of fibrinolytic system; 4. Hemolytic reaction; 5. Leukocyte reaction; 6. Cytokine reaction; ⒎ protein adhesion; B: immune response 1. Complement activation; Humoral immune reaction (antigen-antibody reaction); 3. Cellular immune response. C: tissue reaction ⒈ inflammatory reaction; Cell adhesion, cell proliferation (abnormal differentiation), membrane formation, cytoplasmic transformation, changes in biological reactions, acute systemic reactions such as allergy, toxicity, hemolysis, fever and nerve paralysis, chronic systemic reactions such as toxicity, teratogenicity, immune and dysfunction, and acute local reactions such as inflammation, thrombosis and necrosis. It can be divided into the following three aspects: * metal corrosion * polymer degradation * wear (1) corrosion environment of metal corrosion organisms: (1) salt solution is an excellent electrolyte, which promotes electrochemical corrosion and hydrolysis; ⑵ There are many molecules and cells in the tissue that can catalyze or rapidly destroy foreign components. It will corrode bio-metallic materials. For biomaterials, most of them are local corrosion, including stress corrosion cracking, pitting corrosion, intergranular corrosion, corrosion fatigue and crevice corrosion, which leads to the overall destruction of biomaterials. Although metal materials remain inert in organisms, there may still be substances dissolved in biological tissues, which may cause toxic reactions to biological tissues and cause tissue damage. Such as the toxicity of Cr+6 biological tissue dissolved in stainless steel. (2) In the process of long-term use, due to the influence of oxygen, heat, ultraviolet rays, machinery, water vapor, acid and alkali, microorganisms and other factors, the degraded polymer gradually loses its elasticity, cracks appear, and becomes hard, brittle or soft, sticky and discolored, thus making its physical and mechanical properties worse and worse. Polymers are easy to form fragments, particles and small molecular weight monomer substances when aging, so they must be used with caution. For durable equipment, certain strength and other mechanical properties must be maintained, and aging products must not have toxic effects on surrounding tissues. For example, when medical sutures are degraded, acidic substances will be produced. If the amount is small, it will be easily neutralized by chemicals in the human body. If the aging product is large, it will cause damage to the surrounding tissues. ⑶ Ti6Al4V is a common material for wearing artificial joints. Because the surface is easy to be oxidized to produce TiO2, the wear resistance is poor. After being implanted in human body, wear leads to the formation of dark brown thick matter in the tissues around the joints, causing pain. The average life of titanium alloy total hip arthroplasty is generally less than 10 years. A large number of artificial hip joints are composed of hard metal or ceramic femoral heads and acetabular cups of ultra-high molecular polyethylene, but their life span is less than 25 years. Long-term follow-up data show that the main reason of prosthesis failure is the interface bone dissolution caused by ultra-high molecular polyethylene wear particles, which leads to prosthesis loosening. The foreign body-giant cell reaction caused by the worn particles, also known as granulomatosis, is the main reason for the later failure. Classification characteristics Biomaterials are widely used in classification, with various types and classification methods. Biological materials include metal materials (such as alkali metals and their alloys) and inorganic materials (bioactive ceramics, hydroxyapatite, etc.). ) and organic materials. Organic materials are mainly polymer aggregate materials, and polymer materials are usually divided into synthetic polymer materials (polyurethane, polyester, polylactic acid, polyglycolic acid, lactic glycolic acid polymer and other medical synthetic plastics and rubber, etc.). ) and natural polymer materials (such as collagen, silk protein, cellulose, chitosan, etc. ) according to the material properties; According to the use of materials, these materials can be divided into biologically inert materials, biologically active materials or biodegradable materials. Among polymers, degradable polymers can be divided into bioabsorbable and bioabsorbable according to whether the degradation products can be metabolized and absorbed by the body. According to the influence of materials on blood composition and properties after contact with blood, they can be divided into blood-compatible polymers and blood-incompatible polymers. According to the affinity and reflectivity of materials to body cells, they can be divided into biocompatible and biocompatible polymers. Characteristic biomaterials are mainly used in human body, and their requirements are very strict. They must have four characteristics: (1) biological functionality. It varies with the use of various biomaterials. For example, when used as a sustained-release drug, the sustained-release performance of the drug is its biological functionality. (2) Biocompatibility. It can be summarized as the relationship between materials and living bodies, mainly including blood compatibility and histocompatibility (non-toxic, non-carcinogenic, non-pyrogen reaction, non-immune rejection, etc.). (3) chemical stability. Anti-aging (particularly stable) or biodegradable (controllable degradation). (4) Machinability. Plastic disinfection (ultraviolet sterilization, high pressure boiling, ethylene oxide gas disinfection, alcohol disinfection, etc.). ). Application development performance requirements (1) Biocompatibility Biocompatibility mainly includes blood compatibility and histocompatibility. The material should have no adverse reaction in human body, no coagulation and hemolysis, and no inflammation, rejection and carcinogenesis in living tissue. (2) Mechanical properties materials should have appropriate mechanical properties such as strength, hardness, toughness and plasticity to meet medical requirements such as wear resistance, pressure resistance, impact resistance, fatigue resistance and bending resistance. (3) Anti-biological aging materials should have good chemical stability in vivo and can be used for a long time, that is, they should be able to resist biological corrosion and biological aging while exerting their medical functions. (4) Moldability is easy to process and the price is moderate. Materials are classified according to their functions: * 1, blood compatibility materials such as artificial valve, artificial trachea, artificial heart, plasma separation membrane, adsorbent for hemoperfusion, cell culture matrix, etc. *2. Soft tissue compatible materials, such as polymer materials such as contact lenses, intraocular lenses, polysiloxanes and polyamino acids. , used in artificial skin, artificial trachea, artificial esophagus, artificial ureter, soft tissue repair and other fields; *3. Hard histocompatibility materials, such as medical metal, polyethylene, bioceramics, joints, teeth and other bones; *4, biodegradable materials, such as chitin, polylactic acid, etc. Used for suture, drug carrier, adhesive, etc. ; *5, polymer drug peptides, insulin, synthetic vaccines, etc. For diabetes, cardiovascular diseases, cancer and inflammation. According to the material source classification: * 1, autologous material *2, allogenic organ tissue; *3, allogenic organs and tissues; *4, synthetic materials; *5. Natural materials are divided into * 1, biomedical metal materials * 2, medical polymer materials * 3, and medical inorganic nonmetallic materials. Excellent biomedical metal materials, such as medical stainless steel, cobalt-based alloy, titanium and titanium alloy, nickel-titanium shape memory alloy, precious metals such as gold and silver, amalgam, tantalum and niobium. ⑴ Medical stainless steel has certain corrosion resistance and good comprehensive mechanical properties, and its processing technology is simple. It is the most widely used and widely used biomedical metal material. Commonly used steel grades are US304, 3 16, 3 16 L, 3 17, 3 17L, etc. After medical stainless steel is implanted into living body, pitting corrosion will occur, and occasionally stress corrosion and corrosion fatigue will occur. Preclinical disinfection, electrolytic polishing and passivation of medical stainless steel can improve corrosion resistance. Medical stainless steel is widely used in orthopedics and dentistry. (2) Cobalt-based alloys Cobalt-based alloys generally remain passive in the human body. Compared with stainless steel, the passive film of cobalt-based alloy is more stable and has better corrosion resistance. Among all medical metal materials, it has the best wear resistance and is suitable for manufacturing long-term implants with harsh internal load. In plastic surgery, it is used to manufacture artificial hip and knee joints, as well as bone plates, bone nails, joint fasteners and bone needles. It is used to make artificial heart valves in heart surgery. ⑶ Medical titanium and titanium alloys not only have good mechanical properties, but also have good biocompatibility in physiological environment. Because of its small specific gravity and elastic modulus closer to natural bone than other metals, it is widely used to manufacture various artificial joints such as knees, elbows and shoulders. In addition, titanium alloys are also used in the cardiovascular system. The wear resistance of titanium alloy is not ideal, and there is occlusion phenomenon, which limits its application range. Biomedical polymers are divided into soft tissue materials, hard tissue materials and biodegradable materials according to their application objects and physical properties. It can meet some requirements of human tissues and organs, so it has been widely concerned in medicine. Dozens of polymer materials have been applied to human implant materials. * Soft tissue materials: therefore, they are mainly used as soft tissue materials, especially membranes and pipes for artificial organs. Polyethylene film, PTFE film, silicone rubber film and tube can be used to make artificial lungs, kidneys, hearts, throats, trachea, bile ducts and corneas. Polyester fiber can be used to make blood vessels, peritoneum, etc. * Hard tissue materials: acrylic polymer (i.e. bone cement), polycarbonate, ultra-high molecular weight polyethylene, polymethylmethacrylate (PMMA), nylon and silicone rubber can be used to manufacture artificial bones and artificial joints. * Degradable materials: Aliphatic poly-vinegar has biodegradable characteristics and has been used for acceptable surgical suture. Bio-inorganic nonmetallic materials Bio-inorganic materials mainly include bioceramics, bioglass and medical carbon materials. Bioceramics can be divided into: (1) nearly inert bioceramics such as alumina bioceramics, zirconia bioceramics and borosilicate glass; ⑵ Surface-active bioceramics, such as calcium phosphate-based bioceramics and bioactive glass ceramics; (3) Absorbable bioceramics, such as tricalcium metaphosphate bioceramics and calcium sulfate bioceramics. Bioactive glass ceramics can react chemically with body fluids after being implanted in living body, forming antelope-based apatite layer on the tissue surface, so it can be used for artificial implantation of root, crown, bone filling material and coating material. Compared with natural bone, bioactive glass ceramics have higher strength, but poor toughness, too high elastic modulus, brittle fracture in physiological environment and poor fatigue resistance, so they cannot be directly used in artificial bone with large bearing capacity. Medical carbon material: it has an elastic modulus close to that of natural bone. Medical carbon material has the best fatigue performance, and its strength does not decrease with cyclic load. The disordered stacking of carbon materials has ideal wear resistance. Medical carbon materials are relatively stable, nearly inert and biocompatible in physiological environment, and will not cause coagulation and hemolysis reactions, so they are particularly suitable for use in physiological environment. Medical carbon materials have been widely used in the repair of cardiovascular system, such as artificial heart valves and artificial blood vessels. It can also be used as a coating material for metals and polymers. Biomedical composites Biomedical composites are composed of two or more different materials. According to the substrate, it is divided into biomedical composite materials such as polymer matrix, ceramic matrix and metal matrix. According to the shape and performance of the reinforcement, it can be divided into fiber reinforcement, particle reinforcement and biomedical composite filled with bioactive substances. According to the reaction between tissue and material caused by material implantation, it can be divided into bio-inert, bioactive and absorbable biomedical composites. Performance evaluation of mechanical properties Medical metal is used in human body during stress period, and its stress state is extremely complicated, such as artificial joint, which bears about 3.6× 106 times of load impact and wear every year, which is several times the weight of human body. The mechanical properties of human bones change with age and position. The most important indexes to evaluate the mechanical properties of bones and materials are tensile and compressive strength, yield strength and elastic modulus. Fatigue limit and fracture toughness, etc. Hardness is generally used to reflect the wear resistance of materials in friction parts. Elastic modulus is one of the important properties of biomaterials, and it can't be too high or too low. The modulus is too high relative to the modulus of bone. Under the action of stress, the stressed metal and bone will produce different strains, and the interface between metal and bone will produce relative displacement, resulting in looseness at the interface. After a long time, it will also cause stress inhibition and cause functional degradation and absorption of bone tissue. Too low, large deformation, can not be fixed support. Evaluation criteria The biological evaluation of biomaterials is generally divided according to the use, contact mode, contact position and contact time, but the standards have not been completely unified, and with the transformation of new general biocompatible materials to intelligent biomaterials (such as tissue engineering materials), the standards are still being improved. On the basis of the biological standards put forward by the International Organization for Standardization, countries have kept their own characteristics and basically achieved unity. The existing standards are: 1. Cui O10993.1-1992 to ISO10993.12-1992; American ASTM (F748-82) standard; 13. On the basis of the United States and Japan, China promulgated the "China Standard for Biomedical Materials Influenced by Human Body" by the Ministry of Health on 1997. After being implanted into the human body, it will have an effect and influence on local tissues and the whole body. It mainly includes local tissue reaction and systemic immune reaction. (1) Local tissue reaction (1) Rejection: After the biomaterial is implanted into human body, there may be different degrees of inflammatory reaction around the implant. This is the result of enzymatic hydrolysis and digestion of foreign matter. However, most medical biomaterials are relatively stable and will not be metabolized quickly. At this time, collagen fibers will form a capsule or envelope around the implant, isolating normal tissue from the implant. After the formation of the fibrous capsule, the following changes can occur: the fibrous capsule thickens, which affects the local blood supply and provides a place for accumulation of metabolic products and denatured products; Fibrous capsule calcification or hardening, causing mechanical properties mismatch and pain; Local persistent infection, due to the poor blood supply of fibrous capsule, lack of enough immune cells, slow removal of necrotic cells, so that the infection continues or worsens. ② Calcification: Calcification on the surface of biomaterials often leads to the loss of function of materials. Calcification is caused by both the material itself and the organism, such as the surface properties of the material, the deposition of dead cells, local malnutrition, calcium and phosphorus content in the body, mechanical movement and other factors, all of which are the reasons for producing or accelerating calcification. For soft tissue and cardiovascular implant materials, calcification should be avoided or reduced as much as possible. However, the calcification of implants is beneficial to the repair of bone tissue. For example, surface-active implants made of ceramics and composite materials can prevent interfacial activity by combining calcification with tissues. ③ Infection: Infection is the most common complication of implant materials. In clinical surgery, implanted materials often increase the incidence of infection. On the one hand, the reason is the pollution of materials, on the other hand, the implant material itself has a strong susceptibility to aggravate tissue infection, and the implant material blocks the physiological process of anti-infection by limiting the migration of macrophages; The surface mechanism of some implants or soluble components released by them can interfere with the bactericidal mechanism of macrophages. Therefore, biomedical materials should be strictly sterilized by appropriate methods without affecting their performance. Sterile operation should be strengthened in implantation operation. Avoid implantation failure caused by infection. ④ Blood reaction: mainly thrombosis, which exists in biomedical materials implanted in the circulatory system and in close contact with blood. Therefore, the implanted materials in contact with blood must have excellent anticoagulant properties. ⑤ Tumors: The carcinogenicity of biomaterials is a problem worthy of attention. Although it is rare in clinic, it is very common in animal experiments. It may be related to the following factors: (1) The implanted materials release carcinogens during biological aging; Implant materials are contaminated by carcinogens, and the envelope of L fiber is thickened, which leads to local tissue metabolism disorder and long-term accumulation of metabolites, which increases the possibility of cell mutation. The surface shape of the implant, powdery or spongy materials hardly cause malignant tumors, fibrous materials rarely occur, and only materials with smooth surfaces are easy to occur. Therefore, in the selection and application of materials, avoid using materials that may produce toxic and soluble substances, use materials with rough surfaces as much as possible, and minimize the gap between materials and tissues when implanting. ⑵ Immune response: Some biomaterials can cause systemic immune response after implantation, including humoral immune response and cellular immune response. Clinical studies have found that the occurrence of this immune response is closely related to the activation of complement. For example, polymer materials can be activated through the classical pathway of complement system, and polyester artificial blood vessel materials can be activated through the classical pathway and bypass pathway after implantation. The immune response caused by implanted materials is common in the application of biomedical materials in contact with blood, such as dialysis membranes used in artificial dialysis. Clinically, it can be manifested as allergic reaction, easy infection, high incidence of malignant tumor, calcification or fibrosis of soft tissue, especially pulmonary fibrosis, calcification and arteriosclerosis. There are usually two definitions of the term biomaterial: in a narrow sense, biomaterial refers to natural biomaterial, that is, material formed by biological processes. In a broad sense, biomaterials refer to natural or artificial materials used to replace and repair tissues and organs. Biomaterial science (Materials Science) is a science involving the relationships and laws between the composition, structure, properties and preparation of biomaterials. Its main purpose is to develop bionic high-performance engineering materials and new medical materials for the repair and replacement of human tissues and organs on the basis of analyzing the micro-assembly, biological functions and formation mechanism of natural biomaterials. Its main research contents include: material structure formed by biological process, biomineralization principle, biocompatibility mechanism of materials, self-assembly and self-repair principle of biomaterials.