Plasma Deposition of Polymeric Membranes Applied to Medical Anticoagulant Materials
Keywords Plasma Deposition of Polymeric Membranes Anticoagulant Materials
Investigation of Polymeric Membranes Applied to Blood Anticoagulant Materials
Liu Zhi-jing
(Associate Professor,Department of Astronomy and Applied Physics,University of Science and Technology of China,Hefei 2300, Beijing, China) Technology of China,Hefei 230026)
Key wods plasma deposition, polymeric membranes, blood anticoagulant materials
This paper describes medical applications of polymers in contact with blood and the definition of blood compatible materials. applications and the definition of blood-compatible materials, and discusses the properties and applications of plasma-deposited polymeric membranes, particularly in the context of anticoagulant materials.
I. INTRODUCTION
Some of the plasma processing methods such as deposition, polymerization, sputtering, ion implantation, and cleaning and sterilization are practical and high technology, and are widely used in the sectors of microelectronics, thin films, and materials processing. Plasma chemical vapour deposition and polymerization methods can be used to modify and coat material surfaces to improve the blood compatibility of biomaterials. These methods are applicable not only to inorganic materials such as metals, ceramics and carbon, but also to organic polymer materials. Polymeric materials are widely used in medicine, but there are some disadvantages, such as it causes blood clotting, inflammation and allergic reactions. Therefore, how to improve and enhance the properties of materials (e.g., blood compatibility and anticoagulant properties) so as to overcome these disadvantages remains a key issue in basic research and material preparation. Anticoagulant materials are urgently needed for the fabrication of heart valves, extracorporeal blood circulation devices, artificial blood vessels and other medical devices in contact with blood. The research on anticoagulant materials is regarded as an important symbol of biomaterials research level. Strengthening the research in this area is of great significance to improve the academic status of biomaterials science in China and increase its influence in the international arena [1]. This paper describes the application of polymers in contact with blood, the definition of blood-permeable polymers, the properties and applications of polymer membranes, and the properties of anticoagulant materials.
II. Characterization of plasma deposited polymer membranes
Polymers have been widely used in medicine since the 1950s. Polymer devices in contact with blood include: extracorporeal blood circulation devices, catheters, blood bags and catheters for blood transfusion, renal dialysis devices, plasma removal and plasma detoxification devices, heart valves and vascular grafts. The use of these devices is increasing at a rate of 10% to 20% per year. Among the short-term devices, the most widely used is polyvinyl chloride (PVC), followed by silicone rubber and polyethylene. In dialysis devices, cellulose and its converts, polyamide, polypropylene, polyacrylonitrile, and polyester are the basic film and fiber tube materials. Commercial vascular grafts and heart valves are basically made of polyester mainly polyethylene terephthalate (Dacron) and polytetrafluoroethylene (Teflon) as the basic materials.In the early 1990s, polyethylene urethane ionomers (polyurethanes) and biopolymer materials were developed.The main improvement in polymers in the period from 1980 to 1990 has been the use of medical grades of polymers, which do not release toxic components and carcinogens, and their degradation products are also nontoxic, noncarcinogenic, and do not accumulate in living organisms. Improvements have been made in the permeability and mechanical strength of the membranes and fibrous tubing in the dialysis devices, as well as in the mechanical strength and pore properties of the vascular grafts.
While polymers are widely used, there are still some unsatisfactory aspects. First, the mechanical plasticity (flexibility) of some polymers is inferior to that of naturally occurring vessel walls. This causes turbulence and reduces dialyzability, platelet activity and aggregation [2,3]. Second, some polymers release adjuvants, stabilizers, and plastic particles that can cause blood damage. Thirdly, the degradation products of some polymers cause blood clotting and provoke immune and cellular reactions. In order to overcome these shortcomings, medical practice has been characterized by the use of long-term anti-coagulant adjuvants, such as coumarin (to counteract the effects of vitamin K), and by research into new materials that do not cause blood clotting and immune reactions. Polymeric film materials obtained by plasma deposition and polymerization have particular advantages. These films can be uniformly deposited in materials with complex geometries and even in fiber gaps, and can be combined with almost all substrates such as metals, glass, ceramics, semiconductors, etc., and have good adhesion and efficient cross-linking, which are difficult to synthesize by general chemical methods [4-6]. These polymers can be used as barrier and protective films, which can effectively isolate harmful components to organisms. With the rapid development of the microelectronics industry, plasma processing technology is also more mature, so the preparation and testing of polymer films have become more complete. The properties of these films can be further determined using infrared radiation, nuclear magnetic resonance (NMR) and chemical analysis by electron spectroscopy. The plasma itself has sterilizing properties, which reduces the cost of medical equipment.
The basic requirements for biomaterials are twofold: (1) the material must be able to successfully perform the intended function, and (2) the material must not produce side effects. This requires that the chemical, physical, mechanical, permeability, degradability, strength, and flexibility of the biomaterial must be consistent with the intended function. Medical materials must be subjected to reliable and meticulous testing and strict production standards must be established.
Three, the performance of anticoagulant materials
An important requirement for materials implanted in the body of life is that it can be compatible with the blood without causing coagulation, toxicity and immune response, such materials are known as blood tolerant materials. The ideal hemocompatible polymeric material should be free of the following characteristics:
(1) the polymer releases components or its degradation products into the bloodstream that cause coagulation, inflammation, carcinogenicity, and toxicity;
(2) the polymer lacks mechanical flexibility, which causes turbulence in the bloodstream, with the resultant platelet activity and inflammatory reactions, as well as thrombosis;
(3) the polymer causes inflammatory reactions;
(4) the polymer is not compatible with blood. ) polymers trigger inflammatory reactions and lagging infections.
As seen, hemocompatibility is a multi-parametric function of polymer properties. In this sense, ideal hemotolerant polymers are almost never obtained, and only polymers that partially satisfy the hemotolerance requirement can be obtained. For example, non-toxicity of the released components and degradation products of a polymer can be achieved by using medical grade polymers.
The main pathways of blood coagulation are related to platelets, hemoglobin and fibrin [7, 8]. The anticoagulant properties of synthetic materials are: (1) affinity for blood, (2) inhibition of platelet adhesion and aggregation, (3) occurrence of biofusion reactions, and (4) formation of biomimetic tissue surfaces [9]. Most of the blood components are water, and the hemocompatibility of the materials is largely characterized by hydrophilicity. Plasma deposited membranes show unique advantages. During plasma action, specific chemical reactions take place to form polymer films, whose hydrophilic genes (e.g., -OH, -COOH, etc.) are often exposed, making the films exhibit good hydrophilicity. This property is inherent to the membrane and is not affected by changes in blood concentration or viscosity.
In normal blood vessels, platelet aggregation and release are in dynamic equilibrium, so that thrombi do not normally form. If aggregation exceeds release, a thrombus forms. When a plasma-deposited polymer membrane is used, blood flows across the surface of the membrane, laminar flow is accelerated, eddy currents are less likely to occur, and stagnant point flow is rarely observed. The chance of thrombus formation was greatly reduced compared to the unplasma treated material. Implantation testing of large venous rings in test dogs showed that it also caused a reduction in the intensity and duration of rejection reactions.
The hemocompatibility of the polymer membrane includes no toxic effects on living organisms. For example, they are not toxic to blood cells, do not increase platelet consumption, and do not cause short-lived platelet death. Meaningful results were obtained using the baboon aneroid branching system. The baboon apheresis model is a cluster of small-caliber blood vessels traveling nearly parallel to each other. An artificial blood vessel made of polytetrafluoroethylene was implanted between two vessels in close proximity to each other to form a U-shaped ring of artificial blood vessels. Radioisotope tracing was used to measure the decay rates of labeled platelets in natural and artificial blood vessels, respectively. The results show that the implanted artificial blood vessels have little effect on normal platelet death in baboons, and that the rate of platelet depletion on the surface of the material is independent of the blood flow rate and the total platelet count, and is only linearly related to the length of the artificial blood vessel. Similar results were obtained in both animal and human subjects.
Four, anticoagulant materials
Artificial biomaterials should not activate the coagulation process, the surface of the material in contact with the blood should be able to inhibit the coagulation process, preventing the formation of thrombin. Therefore, a suitable anticoagulant material should be a catalyst to inhibit the coagulation reaction.During the 20 years from 1970 to 1990, different kinds of anticoagulant tablets were developed and widely used. One type of anticoagulant tablet releases a substance, Prostacyclin (PGI2), which prevents platelet aggregation and release, thus controlling the coagulation process. However, it is expensive and unstable. It has a lifetime of only 1 min after hydrolysis under biological conditions, so this biomaterial is of no practical use. Another type of anticoagulant material can be prepared by adding the anticoagulant tablet ingredient dippridamole to the surface of a polymer in contact with blood. For example, pyridine can be added to fibers, cellulose diacetate, nylon, and terephthalic acid **** polymers [10].
The effective anticoagulant properties of this material were demonstrated in material implantation experiments in dogs. Anticoagulant materials were prepared by binding an anticoagulant with strong anionic properties to the surface of a polymer with multiple cations by ionic bonding [11]. Polycationic polymers can be prepared from styrene and its transformations, cellulose, silicone rubber, epoxy resins, polyurethane, or transformations of acrylonitrile and acrylate. Biomaterials release anticoagulants bound by ionic bonds into the blood stream, and the concentration of anticoagulant near the surface is high enough to prevent clot formation for several days. Then the anticoagulant concentration decreases. Therefore, such materials are only suitable for short-term use. Polymer gels can also be used to prepare anticoagulant materials. An ionic coating of anticoagulant captured in the gel prevents clot formation [12, 13]. Spraying urease and a kinase (stroptokinase) onto the surface of polyvinyl chloride and silicone rubber greatly improves the blood compatibility of the materials. However, dissociation of the immobilized enzymes also occurs at the blood surface, thus hindering the long-term use of such materials. Anticoagulant materials can be prepared by combining an anticoagulant with a *** valence on the polymer surface, e.g., hydrogels obtained from polyvinyl alcohol combined with an anticoagulant immobilized by acetal [14], anticoagulants combined with aglycose [15]. A commonly used approach is to chemically activate the polymer by chemical activation or radiochemical activation and then chemically react it with an anticoagulant. For example, isocyanate groups are immobilized onto polystyrene and the resulting polymer is then reacted with an anticoagulant. Similar methods are used to bond anticoagulants to modified polyvinyl alcohol hydrogels, hyperelastomers, poly(hydroxyethyl methacrylate) glycidyl polymers, or cellulose membranes. Chemical or radiochemical treatment leads to the formation of macro groups, which in turn leads to the polymerization of the monomers, and the *** valence bonding of the anticoagulant to the polymer. The surface properties and anticoagulant gene activity of the *** valence-bonded anticoagulants are described in the literature [16, 17], and these preparation methods are reviewed in the literature [18, 19].
Activated carbon has been used in hemodialysis for nearly 30 years, with the disadvantage that the release of pure carbon leads to blood clotting and blood cell damage. However, activated carbon can be treated with plasma to enhance blood compatibility. After the surface of activated carbon particles was coated with a hexamethyldisiloxane (HMDS) film by a plasma deposition process, the HMDS film was shown to be effective in reducing blood cell damage and platelet death by permeation of dog and sheep blood through solid columns of two activated carbons [20]. Amorphous hydride carbon membranes containing varying amounts of fluorine and silicon atoms can be prepared by plasma deposition, and these membranes are highly compatible, with a cell fusion layer observed within 2 d [21]. These membranes can be coated on polyethylene and other plastic substrates as tissue culture materials. Medical polyurethanes together with antimicrobials can be made into functional composites for controlled drug release. If prepared by plasma surface modification, the rate of drug release from these composites is reduced, thereby extending the antimicrobial time without compromising the mechanical strength and flexibility of the material [22]. Poly(methyl methacrylate) (PMMA) was used as a contact lens material as early as in the 1940s, but PMMA has poor hydrophilicity and poor oxygen permeability, and these defects lead to discomfort for the wearer. A plasma polymer film generated by acetylene, nitrogen, and water was applied to the surface of the lens to improve the hydrophilicity of the material and reduce the adhesion of the lens to the corneal epithelial cells. After the oxygen plasma treatment, the oxygen-containing functional groups in the film increased, and the affinity for oxygen increased, thus improving the air permeability. In addition, porous polypropylene films used as carriers for transdermal drug absorption were plasma surface modified to improve surface hydrophilicity and blood compatibility [23].
Plasma deposition, polymerization and treatment technologies are not only applied to anticoagulant materials, but also to ophthalmic materials (e.g., artificial lenses), orthopedic materials, oral materials, drug delivery systems, biosensor materials, and materials and devices for surface cleaning, disinfection and sterilization. In conclusion, plasma deposition and processing technology shows a broad application prospect in biomedical materials.
Lastly, let us briefly discuss some of the limitations of polymer materials applications. In the 70's, the main manifestation was the hemagglutination process, and in the 90's, the main frontiers were the immune reactions induced by implantation of polymers and their long-term use, i.e., lagging infections, allergic reactions, inflammatory reactions, and calcification of the devices. Implantation on rough and porous surfaces carries a high risk of infection. Inflammatory reactions are related to the shape of the implanted device, its mechanical properties and the chemical properties of the polymer. Allergic reactions are currently the main area of research. Poly(methyl methacrylate) (PMMA), metal wires, clamps, nylon sutures, and catheters cause allergic and cellular reactions [24]. The plasma expanders dextran and fibrodextran cause hypersensitivity reactions. Basic research in these areas of the blood coagulation system requires the combined efforts of experts in chemistry, physical chemistry, biochemistry, biology, physics, and medicine and surgery.
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Must be a member, is a paid site, the following is the introduction:
A good anticoagulant biomaterials not only need to have good surface chemical and mechanical properties, but also, more importantly, need to have a good biocompatibility (including histocompatibility and blood compatibility). In order to understand the above properties of anticoagulant biomaterials, it is necessary to characterize them. In this paper, the characterization of anticoagulant biomaterials is discussed from three aspects, i.e., the characterization of the surface chemical composition and structure of anticoagulant biomaterials, the characterization of their mechanical properties, and the characterization of their biocompatibility.