The interaction and influence between biomaterials and human tissues has always been the focus of biomaterials, and it is the basis of biocompatibility research. As a necessary means of medical treatment for modern people, the evaluation of the safety and effectiveness of medical devices is the basis for ensuring the healthy development of China's medical industry. The existing safety and effectiveness evaluation of medical devices is based on the requirements of the GB T 16886 series of standards, and some methods in the standards mainly refer to the inspection methods such as pharmaceutical packaging materials, but due to the great differences between the materials, intended uses, and use methods of medical devices and pharmaceutical packaging materials, coupled with the diversity of medical devices themselves, whether the existing biocompatibility items are sufficient and perfect has become the focus of research in the field of medical device biocompatibility. As the basis of biological experiments, the preparation conditions of samples in biological experiments directly affect the accuracy and validity of test data, and should be paid more attention. Biocompatibility is a theme that runs through the research of biomaterials, and there is no fixed concept. Generally refers to the compatibility between the material and the host, including histocompatibility and hemocompatibility. In a general sense, biocompatibility refers to the various biological, physical, chemical and other reactions produced after the interaction between materials and living organisms, that is, the degree of compatibility between materials and the human body after implantation into the human body. As explained by the ISO meeting"Biocompatibility refers to the ability of living tissues to react to inactive materials. In recent years, the concept of biocompatibility has undergone a great change, and its objects are not only non-reactive materials, but also reactive materials such as tissue engineering. A biomaterial is an exogenous substance to the host, whether it is a surgically implanted device, a building block for regenerative medicine, a vehicle for drug or gene delivery, or a medium to aid in diagnosis or imaging. Regardless of the intended purpose, these biomaterials should not produce significant clinical adverse effects in the host or patient, so the biosafety evaluation of the biomaterials should be carried out. With the development of biomedical engineering, the medical device industry is also advancing rapidly. Many new biomaterials are emerging and are being used in the development and application of medical devices. On the one hand, the structure and composition of various three types of medical device products are becoming more and more complex, especially the external access devices and implantable devices that are in direct contact with the human body have complex structures and diverse materialsOn the other hand, more and more disposable sterile medical devices are used in clinical practice, and they must be aseptically packaged before application, which is easy to cause bacterial endotoxins and other forms of contamination if they are not careful, so the medical risk of such products is getting higher and higher. In order to ensure the safety and effectiveness of the product, a new biomaterial must be evaluated for biocompatibility before entering the clinic, which puts forward higher requirements for the biocompatibility evaluation of biomaterials. Research status of biocompatibility of medical polymer materials 21 Classification of biological materialsThere are many kinds of materials for the production of artificial organs, but the biggest difference between it and ordinary materials lies in the biocompatibility of the materials. Only materials that meet biocompatibility requirements are likely to be used to make artificial organs, often referred to as biomedical materials or biomaterials. Due to the wide variety and different application purposes, there is currently no unified classification standard for biological materials. There are four main types of biomaterials that are widely used today. (1) Medical polymer materials (polymers). Such as thermoplastic, thermoset, synthetic rubber elastomers, synthetic fibers, adhesives, etc. (2) Natural polymer materials. Such as natural rubber, peptides, albumin, silk and so on. (3) Metal materials. Such as metals (titanium, copper, gold, silver, platinum, etc.) and alloy materials (titanium alloys, stainless steels, nichrome, etc.). (4) Inorganic materials. Such as ceramic, carbon, glass, gypsum, etc. 2.2 Research status of biocompatibility of medical polymer materials 22.1 Classification of medical polymer materialsMedical polymer materials, as an important part of biomaterials, started early in China's research, developed rapidly, there are more than 60 kinds of medical polymer materials, more than 400 kinds of products, and nearly 300 tons of polymethyl methacrylate used for medical treatment every year. However, the research of medical polymer materials in China is still in the empirical and semi-empirical stage, and has not yet been established on the basis of molecular design. The progress of modern medicine has become more and more dependent on the development of biomaterials, and medical polymer materials are more widely used as an important part of it, and the demand is also increasing. According to the medical use, it can be mainly divided into: (1) disposable medical polymer materials. Such as infusion instruments, blood bags, various catheters and cannulations, blood collection tubes, polymer bandages, etc. (2) Implantable and interventional materials. Such as artificial blood vessels, artificial heart valves, intraocular lenses, artificial joints, artificial kidneys, artificial lungs, central venous catheters, etc. (3) Materials used for human tissue repair. Such as artificial**, hernia repair sheets, etc. (4) Polymer materials for drugs and controlled drug release. Such as drug-loaded stents, etc. (5) Polymer materials for pharmaceutical packaging. Such as prefillable syringes, pharmaceutical capsules, large infusion bottles, etc. 2.2.2 The technical level of medical polymer materials in China is mainly reflected in the following aspects. (1) It is used for artificial organs, such as heart valves, artificial kidneys, artificial **, hernia tablets, etc. Zhejiang University, Tsinghua University, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, etc. have research groups to conduct relevant research, and they prepare biocompatible materials such as polylactic acid, polyethyllactone, and sodium alginate into scaffold materials by means of multilayer composite, copolymerization, etc. (2) Used in medical devices, such as surgical sutures, urinary catheters, examination instruments, implantable instruments, etc. At present, most of the surgical sutures are derived from silk fibroin, and its fibers not only have excellent biological compatibility, but also have good mechanical strengthThe absorbable sutures are mainly made of polylactic acid, and China has been able to produce these kinds of sutures completely independently, and at the same time has a large market share in China. (3) Used in drug additives, such as drug controlled release carriers, targeted materials, etc. China's research and development in this area is at the forefront of the world, and the polylactic acid ultrafine fiber prepared by researchers from Changchun Institute of Applied Chemistry of the Chinese Academy of Sciences using electrospinning technology can embed oil-soluble and water-soluble drugs and achieve controlled release at the same time. 2.2.3 Biocompatibility Evaluation of Medical Polymer MaterialsThe biocompatibility of research materials involves many aspects (Figure 1). 
Figure 1 Biocompatibility of materials At present, the internationally used safety evaluation items of polymer materials include: cytotoxicity test, ** stimulation test, systemic acute toxicity test, subacute toxicity test, chronic toxicity test, intradermal test, pyrogen test, long-term implantation test, mucosal stimulation test, adhesion and proliferation test of tissue cells, etc. Among them, cytotoxicity test is listed as the preferred test item due to its advantages of simplicity, speed, high sensitivity and animal saving, as an important index to evaluate the toxicity of materials. There are many in vitro cell biocompatibility test methods to evaluate biomaterials, and each has its own characteristics. Although there is a certain correlation between the test methods, it is difficult to achieve complete agreement. Studies have shown that different cytotoxicity evaluation methods have different sensitivities to different biological materials, which may be due to the different toxicological mechanisms of different chemical substances, while the evaluation methods based on different biological endpoints show different sensitivities. In 2005, Weyermann et al. compared three test methods, thiazole blue colorimetric method (MTT method), lactate dehydrogenase release method (LDH method) and neutral red uptake test (NUR test), and studied their toxicity mechanisms, and found that LDH test was sensitive to the destruction of cell membrane integrity, but not sensitive to some toxic substances that affect intracellular activitiesThe MTT test is mainly sensitive to toxicity reactions that affect mitochondrial enzyme activity, and NUR detection is more sensitive to cytotoxicity associated with lysosomal destruction. Therefore, when selecting the test method, it is necessary to reasonably select the contact mode between the sample and the cell and the evaluation index or evaluation method to detect the biological endpoint according to the principle of "closest to the application situation". It will be the development direction of the evaluation of the cell biocompatibility of biomaterials by comprehensively using the molecular level evaluation method to elucidate the mechanism of action of materials on cells and comprehensively evaluate the toxic effect of biomaterials on cells. 2.2.4. The application of new medical polymer materials in medical devices commonly used medical polymer materials, including polymer materials for implantation in the human body: artificial organs such as artificial hearts, artificial blood vessels, etc.;Polymer materials used for **, such as dental, ophthalmology, cosmetic materials and external **polymer materials. With the gradual deepening of the research on the biocompatibility of biomaterials, more and more new biomaterials have entered everyone's field of vision. In terms of organic polymer materials, hydrogels, as a kind of hydrophilic polymer materials that can both swell and insoluble in water, have high water content, good flexibility, strong permeability to small molecules, and therefore have good integration of surrounding tissues, and are more suitable for use as biomedical materials than other types of synthetic materials. Polyvinyl alcohol is the only water-soluble polymer in nature, which has good hydrophilicity, abundant and low cost. Polyvinyl alcohol can be cross-linked by physical, chemical, irradiation, etc., into hydrogel materials with excellent water absorption, swelling, biodegradability and stability, which has broad application prospects in the transplantation, replacement, repair and reconstruction of cartilage, cornea, nucleus pulposus, ** and other tissues. In addition, the hemocompatibility of biomaterials refers to the ability of the surface of biomaterials to inhibit the formation of thrombosis in blood vessels and the effects of biomaterials on blood physiological functions such as hemolysis, decreased platelet function, temporary decrease in leukocytes, decreased function, and complement activation. Some articles have shown that polyester anticoagulant biomaterials and titanium anticoagulant biomaterials have low hemolysis rate, less platelet adhesion, less fibrinogen adsorption, prolonged dynamic coagulation time and recalcification time, and have good hemocompatibility, which is an ideal anticoagulant biomaterial at present. To sum up, the future development of biomaterials can be summarized into four aspects: first, the application prospect of biodegradable polymer materials is broader, and medical biodegradable polymer materials have been highly valued because of their good biodegradability and biocompatibility, whether as sustained-release drugs or as skeleton materials to promote tissue growth, they will be greatly developed. The second is to replicate biomedical materials with the physical and mechanical properties and biological properties of natural tissues of various parts of the human body to achieve the biological functionalization and biological intelligence of polymers, which is an important direction for the development of medical polymer materials. Third, artificial substitute organs will make great progress in the orderliness and compounding of material bodies and surface structures, so as to achieve similar structures and functions to the human body, and their biocompatibility will also be significantly improved. Fourth, the application of pharmaceutical polymers and polymer materials for pharmaceutical packaging will continue to expand. Current status and prospects of biologic research on materials for passive medical devices 31. At present, the types of passive medical devices refer to instruments, equipment, appliances, in vitro diagnostic reagents and calibrators, materials and other similar or related items that are directly or indirectly used in the human body, including the required computer softwareIts effect is mainly obtained by physical means, not pharmacological, immunological or metabolic methods, or although these methods are involved, they only play an auxiliary role. Its purpose is to: (1) diagnose, prevent, monitor, or alleviate diseases;(2) Diagnosis, monitoring, alleviation or functional compensation of injury;(3) Testing, substitution, regulation or support of physiological structures or physiological processes(4) life support or maintenance;(5) Pregnancy control;(6) To provide information for medical or diagnostic purposes by examining samples from the human body. Compared with drugs, medical devices have a wider variety and more complex compositions, including synthetic polymer materials, natural polymer materials, inorganic materials, metal materials and animal-derived tissue engineering materials. Medical devices are divided into active medical devices and passive medical devices according to their structural characteristics. Among them, the use of passive devices includes: liquid medicine delivery and preservation devices;Change of blood, body fluids apparatus;Medical dressings;Surgical instruments;Reuse of surgical instruments;Disposable sterile instruments;Implantable Devices;Contraceptive and family planning devices;Sterilize and clean instruments;Nursing devices, in vitro diagnostic reagents, other passive contact or passive auxiliary devices, etc. 3.2 The basis for the biocompatibility research of passive medical devices and the evaluation of what items can reflect the biocompatibility of materials is a relatively complex system engineering. Many methods and evaluation standards have been formulated at home and abroad, such as ISO 10993 series of international standards, China's GB T 16886 series of standards, etc. Its main spirit is to observe and study the various body reactions caused by long-term and short-term contact with body tissues, cells, and blood after the materials are implanted in the body. 3.3 Current status of biocompatibility research of passive medical devicesDue to the wide variety and wide range of passive medical devices, the research on their biocompatibility has been making rapid progress. In terms of polymer materials, disposable syringes have been widely used in medical institutions, and their quality is closely related to the safety of people's lives. Disposable syringes are devices that are in contact with in vitro and in vivo, and indirectly in contact with blood, and have an action time of Class A (< 24 h) (Table 1). 
The results of the study showed that single-use injection devices have a certain cytotoxicity;Acute systemic toxicity tests, intradermal reaction tests, and delayed hypersensitivity tests were not abnormal. Medical silicone rubber has been widely and important in the fields of life sciences, medical devices, drugs and other fields, but there is still great potential to be tapped, with the development of life sciences and the research of biomaterials, it will make greater contributions to human society. Biopaper is a new type of cross-linked polysaccharide biomaterial, which has been comprehensively evaluated according to the national standard GB T 16886 series of standards for biological evaluation of medical devices, which proves that the material has good biocompatibility. Polylactic acid (PLA) and its copolymers are a class of biodegradable polymer materials, with excellent mechanical properties, chemical stability, high absorption and strength, and its degradation product lactic acid in living organisms can participate in metabolism, and finally generate carbon dioxide and water to be excreted from the body. Referring to the requirements of China's medical device biological evaluation standard (GB T 16886), the biosafety evaluation of the prepared degradable material polylactic acid was carried out from the aspects of pyrogen, cytotoxicity, hemolysis, acute systemic toxicity, intradermal reaction, sensitization reaction, subcutaneous implantation test, hereditary toxicity and subchronic systemic toxicity, and the results proved that the polylactic acid material has good biocompatibility and biosafety, and can be used as a medical material. In recent years, it has been widely used in sustained-release drug carriers, surgical sutures, orthopedic internal fixation plates, bone nails, tissue anti-adhesion materials, tissue engineering cell scaffolds, etc., and plays an irreplaceable role in the fields of anti-tumor, bone defect repair and eye diseases. The advent of bioresorbable implants and their widespread use in minimally invasive surgery have dramatically improved the level of medical care and treatment over the past few decades. A new material: bioresorbable shape memory polymer (BSMP) has good biocompatibility and stable degradation rate in vivo, making it a good polymeric material. 3.4 Prospects for the study of biocompatibility of passive medical devicesOf course, with the progress of society and the development of science and technology, the evaluation methods of biocompatibility are also constantly improving. At present, a new pyrogen detection method is being studied by scholars, namely cell detection method, the method mainly uses human cells in vitro for pyrogen detection, the principle is that pyrogens can cause human cells to release some cytokines related to the heat response, and the content of these factors is quantitatively detected by immunochemical methods to reflect the reaction of its pyrogens, and its advantage is that the detection effect of rabbit method can be achieved without using animals. This method is simple, stable and reliable, and is expected to be a method that can replace the current pyrogen detection methods for quantitative and semi-quantitative detection. Therefore, the use of cells instead of animals for pyrogen testing will become a development trend in the future. In short, with the development of science and technology, especially the development of materials science and life science, the development of new medical device products has been accelerated, and new topics have been put forward for the biological evaluation of medical devices. The key is to scientifically summarize, improve, and correctly apply the IS0 10993 series of standards, grasp the risks of medical devices, and ensure the safety and effectiveness of the use of medical devices. Research status of the influence of extraction conditions on the biocompatibility of passive medical devicesIn the biological test of medical devices, sample preparation is the first step of biological experiment, the premise of successful biological experiment, and the guarantee to ensure the authenticity and reliability of biological experimental results. Series of standards for biological evaluation of medical devices GB T 1688612. The sample preparation conditions are recommended, and the sample extract is often used for testing in biological tests, that is, the test sample is immersed in a suitable medium, extracted under certain conditions, and then a series of biological tests are carried out using the extractable, the purpose of which is to detect the biological reaction that may be caused by the dissolvable substances of medical devices, so as to evaluate the potential harm that the product may cause to patients or users. The biological evaluation standard GB T 16886-12 explains the principle of extraction method, and recommends the extraction vessel, extraction medium, extraction conditions and methods. This method mainly refers to the extraction method of pharmaceutical packaging materials, but because the materials, intended uses, and usage methods of medical devices are very different from pharmaceutical packaging materials, coupled with the diversity of medical devices themselves, testers should choose more reasonable extraction conditions and methods according to the physical and chemical properties of the sample. In Zou Wen et al., it was pointed out that three kinds of polymer materials were suspected reactions after leaching, and two of them were confirmed to be non-hypersensitive reactions and one was a weak allergen after re-excitation. Other biomedical materials such as metals and alloys, ceramics, bioremediation materials, etc., have no hypersensitivity reaction, and the biomedical materials tested under 121,1 h extraction conditions accounted for 804%。Can we think that polymers are more prone to hypersensitivity reactions under the same extraction conditions? At the same time, we also have questions about whether the selection of such extraction conditions is optimal, and whether the extraction conditions of other biomedical materials can fully reflect the biocompatibility of the materialAt the same time, in the biocompatibility study of disposable syringes, it was found that high temperature has a certain effect on this type of material. In the process of making the extract, the extraction medium and extraction conditions used should be suitable for the characteristics and use of the final product and the purpose of use, and the physicochemical properties, dissolvable products or residues of the device material should be considered when selecting the extraction conditions. At the same time, leaching is a complex process, which is affected by time, temperature, surface area to volume ratio, phase equilibrium of the extraction medium and materials, and the influence of high temperature on the extraction kinetics and the constancy of the extraction solution should be considered. In vitro cytotoxicity test is an important part of the current biological evaluation standards at home and abroad, and is a general method for evaluating medical devices that directly or indirectly contact human tissues and cells. The extract test is currently a widely used method to detect the cytotoxicity of medical devices, and the selection of different extraction media may have a direct impact on the test results. There is no relevant literature on the influence of the selection of leaching medium on the evaluation of the in vitro cytotoxicity results of the product and whether there are differences in the evaluation results. At present, the research on what kind of extraction conditions are the most suitable, whether the existing biological evaluation is sufficient, etc., has not been carried out much at home and abroad, probably due to the rapid development of medical device products, the establishment of the medical device biological evaluation system is relatively late, coupled with the diversity of medical devices, there are many types of medical device materials, and the physical and chemical properties are very different. With the development of medical device supervision and management, this contradiction is increasingly revealed. Therefore, by studying the impact of the change of extraction conditions on some biocompatibility items of passive medical devices, especially passive medical devices with polymer materials as raw materials, the biocompatibility of passive medical device materials in China can be effectively improved.
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