Biomaterials (biomaterials) is used to contact and interact with the living system, and can diagnose and treat its cells, tissues and organs, replace and repair or induce regeneration of a class of natural or synthetic special functional materials, also known as biomedical materials. Biomaterials is the field of materials science in the development of a variety of disciplines cross-penetration of the field, its research involves materials science, life sciences, chemistry, biology, anatomy, pathology, clinical medicine, pharmacology and other disciplines, but also involves the scope of engineering technology and management science. Biomaterials include synthetic and natural materials; single materials, composite materials, and hybrid materials made by combining living cells or natural tissues with inanimate materials. Biomaterials themselves are not drugs, and their therapeutic pathways are characterized by direct combination and interaction with biological organisms.
Basic introduction Chinese name ：Biological materials Foreign name ：Biological materials Time ：The nineties Characteristics ：Broad development prospects Discipline ：Biology Development,Introduction,Principle,Related products,Properties,Functionality,Compatibility,Compatibility reaction,Host reaction,Material reaction,Classification Characteristics,Classification,Characteristic,Sets of development,Performance requirements,Material classification. Performance Evaluation,Mechanical Properties,Evaluation Criteria,Human Influence,Terminology,Definition,Materials Science,Development Since the late 90's, the world's biomaterials science and technology has been developing rapidly, even in today's global economic downturn, biomaterials are still maintained at a high rate of growth of 13% per annum, which fully reflects its strong vitality and broad prospects for development. Modern medicine is developing in the direction of regeneration and reconstruction of damaged human tissues and organs, restoration and enhancement of human physiological functions, personalized and minimally invasive treatment. Traditional inanimate medical metals, polymers, bioceramics and other conventional materials can no longer meet the requirements of medical development, biomedical materials science and engineering is facing new opportunities and challenges. In the future, the market share of biomedical materials is likely to catch up with drugs. Therefore, it is imperative to strengthen the clinical application research and promotion of biomedical materials, and to focus on the development of China's biomedical materials research, development, production and marketing of closely integrated system. In fact, the country's current basic research in biomaterials science has made significant breakthroughs in the world's advanced ranks, but the level of industrialization has yet to be improved, the industry is small, the development of relatively lagging behind, and can not meet the actual needs of universal health care. Under the strong support of national policy and economy, the industrialization of biomaterials in China will speed up. Enterprises should enhance the ability of independent innovation, further solve the situation of relying on imports, and at the same time increase the export efforts to achieve leapfrog development and expand the influence of Chinese biomaterials products in the international arena. Introduction Principle Biological materials (Biological materials), also known as biotechnology or biotechnology. It is a comprehensive science and technology that applies the principles of biology and engineering to form new varieties of organisms with specific traits by orienting the unique functions of biomaterials and organisms. Bioengineering was developed in the early 70's on the basis of molecular biology, cell biology, etc., including genetic engineering, cell engineering, enzyme engineering, fermentation engineering, etc., which are interconnected with each other, with genetic engineering as the basis. Only through the genetic engineering to modify the biology, it is possible to produce more and better biological products according to the desire of human beings. And the results of genetic engineering can only be transformed into products through fermentation and other engineering. Related products In medicine, a large number of inexpensive drugs to prevent and control human diseases can be produced through bioengineering, such as into insulin, interferon, growth hormone, hepatitis B vaccine and so on. Bio-engineering in food, light industry in the application of the surface is also very wide. 1983 the United States with bio-engineering production for the production of beverages used to make high fructose syrup annual output of 6 million tons, so that the consumption of sucrose reduced by half. The adoption of bioengineering technology has brought about great changes in breeding, such as the transfer of disease-resistant genes to tobacco, which has produced new varieties of tobacco to prevent pests; and the transfer of nitrogen-fixing genes of the lower organisms, rhizobium, to the cells of the higher crops to enable them to manufacture nitrogen fertilizers on their own, which has also achieved certain results. Countries all over the world attach great importance to bioengineering, and China has also listed bioengineering as one of the key scientific research projects for development. The research of bioengineering will have a great impact on the production mode and life style of human beings. Properties Functionality refers to a series of properties that a biomaterial should have when it possesses or accomplishes a certain biological function. They are mainly categorized according to their uses: * Functions to bear or transmit loads. Such as artificial bones, joints, and teeth, etc., predominantly * Functions to control the flow of blood or body fluids. Such as artificial valves, blood vessels, etc. *Electricity, light, and sound conduction functions. Such as cardiac pacemakers, artificial lenses, cochlear implants, etc. *Filling function. Such as cosmetic surgery fillers, etc. Compatibility refers to the ability of a biomaterial to perform its function effectively and for a long period of time within a living organism or on the surface of the body. It is used to characterize the biological behavior of biomaterials interacting with the organism in the organism. According to the site of contact between the material and the organism, it is classified as: *Hematocompatibility. The material is used in the cardiovascular system in contact with [[blood]], and is primarily examined for interactions with blood *Contact with extracardiovascular tissues and organs. Examines primarily interactions with tissues, also known as general biocompatibility * Mechanical compatibility. Examines the consistency of mechanical properties with the organism Biomaterials and Nanobiotechnology is an international, interdisciplinary, English-language publication of original literature on the preparation, properties, and evaluation of biomaterials for research, distributed by Scientific American Press. Covers physical, chemical, toxicological, electrochemical, mechanical and optical properties of nanomaterials, suites for biotechnology (pharmaceuticals, drug delivery systems, cosmetics, food technology, biotransformation, renewable energy and energy storage, biosensing, nanomedicines, tissue engineering, implantable medical devices, biophotonics, nanophotodynamic therapies, oncology). Compatible reactions Host reactions (1) Biological reactions A: Blood reactions ⒈ Platelet thrombus; ⒈ Coagulation system activation; ⒈ Fibrinolytic system activation; ⒈ Fibrinolytic system activation; ⒈ Complement activation; ⒈ Humoral immune reaction (antigen-antibody reaction); ⒈ Cellular immune reaction. C:Tissue response ⒈ inflammatory response; ⒈ cell adhesion ⑶ cell proliferation (abnormal differentiation) Singed membrane formation ⑶ careful cytoplasmic transformation (2) Changes in organisms in response to organisms ⒈ Acute systemic response Allergy, toxicity, hemolysis, fever, nerve paralysis, etc. ⒈ Chronic systemic response Toxicity, teratogenesis, immunity, dysfunction, etc. ⑶ Acute local response Inflammation, thrombosis, necrosis, exclusion, etc. Singed Chronic local response Carcinogenicity, calcification, Inflammation, ulcers, etc. Material reactions Biological organisms act on biological materials - material reactions, the results of which can lead to structural damage and change in the properties of the material and loss of its function. They can be categorized into the following three areas: *Metal corrosion *Polymer degradation *Wear and tear (1) Metal corrosion Corrosive environments in living organisms: (1) Salt-containing solutions are excellent electrolytes, promoting electrochemical corrosion and hydrolysis; (2) A wide variety of molecules and cells exist in tissues with the ability to catalyze or rapidly destroy foreign components. Corrosion will occur on biometallic materials. For biological materials are mostly localized corrosion, specifically including stress corrosion cracking, pitting corrosion, intergranular corrosion, corrosion fatigue, and crevice corrosion, which leads to the overall destruction of biological materials. Although the metal material remains inert in the organism, but there may still be substances dissolved into the biological tissues, and the biological tissues produce a toxic reaction, resulting in tissue damage. For example, the toxicity of Cr+6 dissolved in stainless steel biological tissues. (2) polymer degradation Polymer in the process of long-term use, due to oxygen, heat, ultraviolet light, mechanical, water vapor, acid and alkali and microorganisms and other factors, and gradually lose elasticity, cracks, harden, brittle or soft, sticky, discoloration, etc., so that it is the phenomenon of physical and mechanical properties are getting worse. Polymer aging is easy to form fragments, particles, small molecular weight monomer material, so it must be used with caution, the durability of the device, must maintain a certain level of strength and other mechanical properties, the aging product can not be toxic to the surrounding tissue. For example, medical suture degradation will produce acidic substances, if the amount is small, it is easy to be neutralized by the body's chemical substances, if the aging product is larger, it will cause damage to the surrounding tissues. (3) Wear and tear The commonly used material for artificial joints is Ti6Al4V, which has poor abrasion resistance due to the easy oxidation of the surface to generate TiO2, and after implantation in the human body, wear and tear causes the formation of a black-brown consistency in the tissues around the joints, which in turn causes pain. The average lifespan of titanium artificial total hip joints is generally less than 10 years. A large number of artificial hip joints are made from a combination of a hard metal or ceramic femoral head and an ultra-high polymer polyethylene acetabular cup, yet it also has a lifespan of no more than 25 years. Long-term follow-up data show that the main cause of prosthesis failure is interfacial osteolysis caused by UHMWPE wear particles, which leads to loosening of the prosthesis. This foreign body-giant cell reaction caused by wear particles, also known as granulomatosis, is the most significant cause of late failure. Classification Characteristics Classification Biomaterials sets are widely used and come in many varieties, and there are many ways to categorize them. Biomaterials include three main categories: metallic materials (such as alkali metals and their alloys, etc.), inorganic materials (bioactive ceramics, hydroxyapatite, etc.), and organic materials. Organic materials are mainly polymer aggregates materials, polymer materials are usually divided into synthetic polymer materials (polyurethane, polyester, polylactic acid, polyglycolic acid, lactic acid glycolic acid *** polymer and other medical synthetic plastics and rubbers, etc.), natural polymer materials (eg, collagen, silk proteins, cellulose, chitosan, etc.); according to the use of the material, these materials can be divided into bioinert ( According to the use of materials, these materials can be divided into bioinert, bioactive or biodegradable materials. Among polymers, according to whether the degradation products can be metabolized and absorbed by the body, degradable polymers can be divided into bioabsorbable and bioinabsorbable. According to the material and blood contact on the blood composition, properties of the state is divided into blood-compatible polymers and blood-incompatible. According to the affinity and reflection status of the materials on the cells of the body, they can be divided into biocompatible and bioincompatible polymers and so on. Characteristics Biomaterials are mainly used in human beings, and their requirements are very strict, and they must have four characteristics: (1) Biofunctionality. Varies depending on the use of various biomaterials, e.g., when used as a slow-release drug, the slow-release performance of the drug is its biofunctionality. (2) Biocompatibility. Can be summarized as the interrelationship between the material and the living body, mainly including blood compatibility and histocompatibility (non-toxicity, non-carcinogenicity, no pyrogenic reaction, no immune rejection, etc.). (3) Chemical stability. Resistance to biological aging (particularly stable) or biodegradability (controlled degradation). (4) Processability. Capable of molding and disinfection (ultraviolet sterilization, autoclave boiling, ethylene oxide gas disinfection, alcohol disinfection, etc.). Set development Performance requirements ⑴ Biocompatibility Biocompatibility mainly includes blood compatibility, tissue compatibility. Materials in the human body requires no adverse reactions, does not cause coagulation, hemolysis phenomenon, living tissue does not occur inflammation, rejection, carcinogenicity and so on. (2) Mechanical properties The material should have appropriate strength, hardness, toughness, plasticity and other mechanical properties to meet the wear resistance, pressure resistance, impact resistance, fatigue resistance, bending and other medical requirements. (3) biological aging resistance materials in the living body to have good chemical stability, can be used for a long time, that is, in the performance of its medical function at the same time to be resistant to biological corrosion, biological aging. (4) Forming and processing performance Easy to form and process, affordable. Material classification by material function: *1, blood-compatible materials such as artificial valves, artificial trachea, artificial heart, plasma separation membrane, blood perfusion with adsorbent, cell culture substrate, etc.; *2, soft tissue compatible materials such as invisible eye piece of polymer materials, artificial lenses, poly-silicone, poly-amino acid, etc., used in the field of artificial skin, artificial trachea, artificial esophagus, artificial ureter, soft tissue repair, etc.; *3, hard tissue compatible materials such as polymer materials, artificial lens, poly-silicone, polyamino acid, etc., used for the artificial skin, artificial trachea, artificial esophagus, artificial ureter, soft tissue repair etc.; *3, hard tissue compatibility materials such as medical metal, polyethylene, bioceramics, etc., joints, teeth, other bones, etc.; *4, biodegradable materials such as chitin, polylactic acid, etc., used for sutures, drug carriers, adhesives, etc.; *5, polymer drug peptides, insulin, synthetic vaccines, etc., used for diabetes, cardiovascular, cancer, and inflammation, etc.. Classified according to the source of materials: *1, autologous materials *2, homologous organs and tissues; *3, allogeneic organs and tissues; *4, synthetic materials; *5, natural materials According to the composition and nature of the following: * 1, biomedical metal materials * 2, medical polymers * 3, medical inorganic non-metallic materials Bio-medical metal materials The better biomedical metal materials, medical stainless steel, cobalt-based alloys, titanium and titanium-based alloys, titanium and titanium-based materials, medical stainless steel, cobalt-based alloys, titanium and titanium-based alloys, titanium and titanium-based materials. The better biomedical metal materials include medical stainless steel, cobalt-based alloys, titanium and titanium alloys, nickel-titanium shape memory alloys, gold, silver and other precious metals, silver amalgam, tantalum, niobium and other metals and alloys. (1) medical stainless steel has a certain degree of corrosion resistance and good overall mechanical properties, and processing technology is simple, is the most widely used in the set of biomedical metal materials, the most widely used materials. Commonly used steel grades are US304, 316, 316 L, 317, 317L and so on. Medical stainless steel implanted in a living body, pitting corrosion may occur, and occasionally produce stress corrosion and corrosion fatigue. Preclinical sterilization, electrolytic polishing and passivation of medical stainless steel can improve corrosion resistance. Medical stainless steel in orthopedic surgery and dentistry set more. (2) cobalt-based alloys cobalt-based alloys in vivo generally remain passivated, compared with stainless steel, cobalt-based alloys passivation film is more stable, better corrosion resistance. In all medical metal materials, its wear resistance is the best, suitable for manufacturing in vivo bearing harsh long-term implants. In orthopedic surgery, it is used to manufacture artificial hip and knee joints as well as bone plates, bone nails, joint buckles and bone pins. In cardiac surgery, it is used to manufacture artificial heart valves. (3) medical titanium and titanium alloy not only has good mechanical properties, but also in the physiological environment has good biocompatibility. Because of its small specific gravity, modulus of elasticity is closer to natural bone than other metals, it is widely used in the manufacture of a variety of can, knee, elbow, shoulder and other artificial joints. In addition, titanium alloy is also used in the cardiovascular system. Titanium alloy wear resistance is not ideal, and the existence of occlusion phenomenon, limiting the scope of its use. Biomedical polymer According to the set of objects and material physical properties are divided into soft tissue materials, hard tissue materials and biodegradable materials. It can meet some of the requirements of human tissues and organs, and thus has been widely valued 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 the membranes and tubes of artificial organs. Polyethylene membrane, polytetrafluoroethylene membrane, silicone rubber membrane and tube, can be used to manufacture artificial lungs, kidneys, heart, larynx, trachea, bile ducts, cornea. Polyester fibers can be used to make blood vessels, peritoneum, etc. * Hard tissue materials: acrylic polymer (i.e. bone cement), polycarbonate vinegar, ultra-high molecular weight polyethylene, polymethyl methacrylate methyl ester (PMMA), nylon, silicone rubber, etc. can be used to manufacture artificial bone and artificial joints. * Degradable materials: Aliphatic polyvinyl acetate has biodegradable properties and has been used for receivable surgical sutures. Bio-medical inorganic non-metallic materials Bio-inorganic materials mainly include bio-ceramics, bio-glass and medical carbon materials. According to the implantation of living organisms caused by tissue and material reactions, bioceramics are divided into: (1) nearly inert bioceramics, such as alumina bioceramics, zirconia bioceramics, borosilicate glass; (2) surface-active bioceramics, such as calcium phosphate-based bioceramics, bioactive glass ceramics; (3) absorbable bioceramics, such as tricalcium metaphosphate bioceramics, calcium sulfate bioceramics. Bioactive glass ceramics implanted in the living body, can be chemically reacted with body fluids and generate an antelope-based apatite layer on the tissue surface, so they can be used for artificial implant roots, crowns, bone fillings and coating materials. Compared with natural bone, bioactive glass ceramics have high strength, but poor toughness, high modulus of elasticity, easy to brittle, in the physiological environment of the anti-fatigue performance is poor, can not be directly used for bearing force larger artificial bone. Medical carbon material: has a modulus of elasticity close to that of natural bone. Medical carbon material fatigue performance is optimal, strength does not decline with cyclic loading. Unorganized stacked carbon materials have ideal wear resistance. Medical carbon materials are more stable and nearly inert in physiological environments, have better biocompatibility, do not cause coagulation and hemolytic reactions, and are particularly suitable for use in physiological environments. Medical carbon materials have been used in large quantities for the repair of the cardiovascular system, such as artificial heart valves and artificial blood vessels. They are also used as coating materials for metals and polymers. Biomedical composites Biomedical composites are composites of two or more different materials. According to the substrate is divided into: polymer-based, ceramic-based, metal-based biomedical composites. According to the form and nature of the reinforcement is divided into fiber reinforced, particle reinforced, biologically active substances filled biomedical composites. According to the tissue and material reaction caused by the implantation of the material is divided into: bioinert, bioactive and absorbable biomedical composites. Performance Evaluation Mechanical Properties Medical metal as a force during the service in the human body, its force state and its complexity, such as artificial joints, to withstand about 3.6 × 106 times a year, and several times the weight of the body load impact and wear. The mechanical properties of human bone vary according to age and location, and the most important indicators for evaluating the mechanical properties of bone and materials are: tensile and compressive strength, yield strength, modulus of elasticity. Fatigue limit and fracture toughness, etc. For materials with friction parts, hardness is generally used to reflect their wear resistance. Modulus of elasticity is one of the important properties of biomaterials, too high or too low. Modulus relative to the bone is too high, under the action of stress, the metal and bone under stress will produce different strains, in the metal and bone contact surface will appear relative displacement, resulting in loosening at the interface; long time, it will also result in stress prohibition, causing functional degradation and resorption of bone tissue. Too low, the deformation is large, and it can not play the role of fixation and support. Evaluation standards Biological evaluation of biomaterials is generally divided according to the use, contact mode, contact with human body parts and contact time, etc. However, the standards have not yet fully realized unification, and with the new general biocompatible materials to intelligent biomaterials (such as tissue engineering materials), the standards are still being improved. Countries have been basically unified in the International Organization for Standardization proposed biological standards, retaining their own characteristics. The existing standards are: ⒈ ISO10993.1-1992 to ISO10993.12-1992; ⒉ U.S. ASTM (F748-82) standards; ⑶ China in the United States and Japan on the basis of the Ministry of Health in 1997 issued by the Chinese standards Human impact Biomaterials implanted in the human body will have effects and impacts on local tissues and the whole body. It mainly includes local tissue reaction and systemic immune reaction. (1) Local tissue reaction ① Rejection reaction: after implantation of biomaterials in human body, inflammatory reaction of different degrees can occur around the implanted material. This is the result of the body's enzymatic digestion of the foreign material. However, most medical biomaterials are relatively stable and will not be metabolized quickly. This is when collagen fibers surround the implant to form a periosteum, or capsule, separating normal tissue from the implant. The following changes can occur after the formation of the fibrous capsule: thickening of the fibrous capsule, thus affecting the local blood supply and providing an accumulation site for the body's metabolic products and material denaturation products; calcification or hardening of the fibrous capsule, resulting in mismatch of the mechanical properties and pain; persistent local infections, which persist or worsen due to the poor blood flow of the fibrous capsule, lack of sufficient immune cells, and slower clearance of necrotic cells. ② Calcification: the formation of calcification on the surface of biomaterials often leads to loss of function of the material. Caused by calcification of the material itself, but also the causes of the organism, such as the surface nature of the material, the deposition of dead cells, local malnutrition, the body's calcium and phosphorus content, mechanical movement and other factors, are produced or accelerated by the cause of calcification. For soft tissue and cardiovascular implant materials, calcification should be avoided or minimized as much as possible. And the calcification of the implant *** is beneficial to the repair of bony tissues, such as ceramics, as well as composite materials prepared by the surface-active implants, through calcification and tissue bonding, which prevents interface activity. ③ Infection: Infection is the most common complication of implanted materials. Implanted materials often increase the incidence of infection in clinical procedures. The reason for this is, on the one hand, the contamination of the material, on the other hand, the implanted material itself has a strong aggravation of the susceptibility of the tissue to infection, the implanted material by restricting the migration of macrophages, blocking the physiological process of anti-infective; some implants of the table machine or its release of soluble components, can interfere with the bactericidal mechanism of the macrophage, and so on. Therefore, biomedical materials should be strictly sterilized by appropriate methods without affecting their performance. Their implantation procedures should enhance aseptic operation. Avoid implantation failure due to infection. ④ Blood reaction: mainly thrombosis, seen in biomedical materials implanted in close contact with blood in the circulatory system. Therefore, implantation materials in contact with blood must have excellent anticoagulant properties. ⑤ Tumors: The carcinogenicity of biomaterials is a compelling issue. Although it is extremely rare in the clinic, it is common in animal experiments. It may be related to the following factors: the release of carcinogenic substances from the implanted material in the process of biological aging; the implanted material is contaminated by carcinogenic substances l The thickening of the fiber envelope leads to local tissue metabolism obstacles, long-term accumulation of metabolites, and an increase in the likelihood of cellular mutation; the surface shape of the implant, the powdered or spongy material is almost unlikely to malignant tumors, and the fibrous material is rarely occurring, and only the smooth surface of the materials are prone to occur. Therefore, in the selection and application of materials, avoid the use of materials that may produce *** sex, or even toxic soluble substances, use rough surface materials as much as possible, and minimize the gap between materials and tissues during implantation. (2) Immune response: some biological materials can lead to systemic immune response after implantation, including humoral 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 the complement system, and polyester artificial blood vessel materials can activate complement through the classical pathway and the bypass pathway after implantation. The immune reaction caused by implanted materials is commonly found in biomedical materials that are set in contact with blood, such as dialysis membranes used for artificial dialysis. Clinically, they can manifest as allergic reactions, susceptibility to infection, high incidence of malignancy, calcification or fibrosis of soft tissues, especially pulmonary fibrosis, calcification and atherosclerosis. Term Definition Biomaterials are usually defined in two ways: in a narrow sense, biomaterials are natural biomaterials, that is, materials formed by biological processes. In the broader sense, biomaterials are natural or man-made materials that are used to replace and repair tissues and organs. Materials science Biomaterials science is the science that deals with the interrelationships and laws governing the composition structure, properties and preparation of biomaterials. Its main purpose is to develop bionic high-performance engineering materials and new medical materials for human tissue and organ repair and replacement based on the analysis of micro-assembly of natural biomaterials, biological functions and formation mechanisms. Its main research content are: biological process formation of material structure, the principle of biomineralization, the mechanism of material biosolubility, biomaterials independent assembly, self-repair principle.