Biodegradable materials and their applications in biomedicine
With the continuous development of medical technology and the increasing improvement of people’s living standards, various types of medical materials have begun to be widely used in human tissues. The compatibility, blood compatibility and degradability between medical materials and human tissues People pay more and more attention to other issues. The following is a systematic analysis and discussion on the application of biodegradable materials in the biomedical field. First, a preliminary analysis is made on the degradation principle of biodegradable materials, and then the common biodegradable materials in the biomedical field are analyzed according to the process and source standards. Classify and introduce the application of some typical materials in biomedicine.
1. Degradation principle of biodegradable materials
Biodegradable materials interact with the biological environment of various factors such as body fluids, organic macromolecules, enzymes, free radicals, cells, etc., and gradually degrade into low molecular weight compounds through a series of reactions such as hydrolysis, enzymolysis, and oxidation. monomer. After absorption, digestion, and metabolic reactions, the degradation products are excreted from the body or participate in the normal metabolism of the body to be absorbed by the body to complete the degradation process. If the body fluid enters the biological material from the tissue or a certain component of the biological material is dissolved in the body fluid, the material will expand due to the increase in volume and exudate its own substance. This process destroys the hydrogen bond and van der Waals force of the material itself. , Will cause cracks or voids in the material, and eventually the material will gradually undergo chemical degradation in the biological environment. In clinical practice, people hope that the implanted biodegradable materials will also complete the differentiation and degradation reactions during the biological tissue treatment period according to the same procedure, so as to avoid the body's inflammation or stress response due to the implanted materials. We know that the treatment time for skin tissue is usually within 3 to 10 days, the treatment time for visceral tissue is usually between 1 and 2 months, and the treatment time for large organ tissues often takes 6 months or more. After biodegradable biomaterials are implanted in the human body, their degradation performance and degradation products have a great impact on the biological environment, material reactions and human body reactions. The slow degradation rate or the long residence time of degradation products can easily cause inflammation in human tissues. , Thrombosis and other adverse reactions. Studies [6] have shown that the degradation process and progress of most biodegradable materials are inconsistent with the best expected results. Therefore, in the research and clinical application of biodegradable materials, the degradation-related issues of biodegradable materials must be treated with caution, especially the degradation rate and degradation products.
2. Basic classification and application of biodegradable materials
Biodegradable materials are used in the human body and must meet strict conditions in terms of the material itself and its effects on the human body: easy to process, low price, easy to sterilize, definite degradation time, biological stability and mechanical properties to meet the needs of the implantation site , Good histocompatibility, blood compatibility and mechanical compatibility, no pyrogen reaction, genetic toxicity, teratogenicity and carcinogenicity, no irritation and sensitization.
At present, biodegradable materials can be classified according to different processes and sources, including natural polymer degradable materials, microbial synthetic degradable polymer materials, and chemically synthesized degradable polymer materials [3,9]. The specific classification and application are summarized as follows:
1. Natural polymer biodegradable materials
Currently, the most commonly used natural polymer biodegradable materials in the biomedical field mainly include gelatin, collagen, polysaccharides, and silk fibroin.
(1) Gelatin material
Gelatin is mostly derived from mammalian skin, bone, tendon, tail and other tissues. Its most notable feature is water-soluble polymer, which slowly expands and softens after absorbing water, and has biocompatibility, gelation, and biodegradability. Utilizing the characteristics of gelatin, easy to form, degradable by enzymes, and easy to be absorbed by the human body, it can be used as a slow-release material in drug carriers, excipients or slow-release shells; because of its good air permeability and water permeability As a wound dressing and artificial skin material, it can prevent fluid from the wound or the occurrence of secondary infection symptoms; in addition, gelatin plasma substitutes are degradable, non-toxic and non-immunogenic, etc. Clinical advantage.
(2) Collagen
Collagen is the main component of connective tissue, which accounts for about 1/3 of the protein content in animals. It is mainly found in animal tissues, skin, ligaments and cartilage. It has the functions of supporting body organs, maintaining mechanical stability, elasticity and strength. As a natural biological resource, it has the characteristics of good biocompatibility, low immunogenicity and biodegradability; clinical use has shown that collagen can significantly promote the repair, regeneration and reconstruction of defective tissues; but it lacks sufficient The mechanical strength can be improved by cross-linking modification or composite use with other biological materials]. At present, collagen has been widely used in the preparation of biodegradable sutures, hemostatic agents and wound dressings, biological patches, bone repair materials, hemodialysis membranes, hemostatic agents, drug release carriers, and as tissue engineering scaffolds, various ophthalmic treatments Devices and other aspects. However, in view of the complexity of clinical issues and the need for product upgrades, there are still many problems to be solved in the application research of collagen, such as the potential immune response of heterologous collagen, the possible cytotoxicity of residual cross-linking agent, and implantation. The mechanical strength and degradation controllability of collagen-like products.
(3) Polysaccharide materials
Polysaccharide materials are mostly derived from starch, hyaluronic acid, heparin, chitin and other ingredients, and their biocompatibility and biodegradability are very ideal. In nature, chitin is rich in content and is a large class of important polysaccharides except cellulose. It is non-toxic and has no side effects. It has good affinity for human cells, does not cause rejection, and has good biocompatibility and Degradability. In addition, it also has the characteristics of antibacterial, antiviral, antitumor, promoting wound healing and strong adsorption capacity. Because chitin contains many polar groups such as hydrogen bonds and has high crystallinity, it is insoluble in acid and alkali, and insoluble in water, so it is difficult to be used by the body. However, chitin can be dissolved in dilute acid and body fluids after being deacetylated into chitosan, and can be used by the human body. Chitin and chitosan have high chemical reactivity, and their derivatives after amidation, carboxylation, cyanation, acidification and other modifications are widely used in the medical field, such as hemostatic agents, flocculants, absorbable surgical sutures , Artificial skin, wound dressings, slow-release agents of anti-cancer drugs or chemotherapeutics, immobilized enzyme carriers, separation membrane materials, etc.
(4) Silk fibroin
Silk fibroin is mostly derived from silk and contains very rich amino acids inside, so it has good biocompatibility, and has been proven to be non-allergenic or carcinogenic, with excellent transparency and air permeability, and good film-forming effect. However, due to the molecular structure of silk fibroin, the hydrophilicity of silk fibroin and the mechanical properties after film formation are not good. Through the blending modification method, the hydrogen bonds and other forces formed between the mixed macromolecules and silk fibroin are Inducing silk fibroin molecules to change the structure can effectively improve the mechanical properties, thermal properties and water solubility of silk fibroin materials. At present, in the field of biomedicine, it is widely used in wound coating materials, artificial skin, artificial tendon ligaments, contact lenses, drug carriers, artificial blood vessel carriers and other fields.
2. Microbial synthesis of degradable polymer materials
Microbial synthesis of degradable polymer materials refers to the use of certain organic matter (such as glucose or starch) as a food source to synthesize carbon source organic matter into a polyester with differentiable characteristics under a series of complex reactions such as the fermentation of micro organisms Or polysaccharide polymers. At present, microbial synthetic polymer biodegradable materials widely used in clinical practice mainly include two types: biopolyester (PHA) and polyhydroxybutyl ester (PHB). Take PHB as an example. PHB is a high molecular polymer synthesized by microbial cells. Its structure and performance are different from natural macromolecular degradable materials, but more similar to aliphatic polyester polymers, with natural and chemical synthesis degradable The advantage of polymer, the degradation products are finally excreted as carbon dioxide and water through metabolism, without any toxic substances that may be produced by the synthesis of chemical raw materials. In addition, Tang Suyang and other studies have shown that PHB has excellent biocompatibility. At present, it has been widely used in absorbable surgical sutures, orthopedic materials, and drug control systems.
3. Chemical synthesis of degradable polymer materials
Compared with natural polymers, biodegradable polymer materials synthesized by chemical methods can be selected according to the needs of actual applications, by selecting appropriate monomers, or by controlling the reaction conditions in the synthesis process, or performing simple and low-cost Physical or chemical modification, etc., to design and adjust its structure and performance to achieve the purpose of synthesizing the target material. For example, through chemical control methods, the strength, degradation rate, microporous structure and permeability of polymer materials can be improved to expand the application field. In the chemically synthesized biodegradable polymers currently developed and researched, the main chain generally contains hydrolyzable ester groups, amido groups or urea groups. The following is the most researched and most widely used type of chemically synthesized degradable polymer materials in the current clinical biomedical practice—aliphatic polyester materials, such as polyglycolide (PGA), polylactic acid (PLA), and polylactic acid -Glycolic acid copolymer (PLGA), polycaprolactone (PCL), etc. will be introduced.
(1) Polyglycolide (PGA)
PGA is the linear aliphatic polyester with the simplest structure. It uses glycolic acid as the basic source and has a wide range of raw materials, mainly sugar beet, immature grape juice and sugar cane. Among the existing biodegradable polymers, the degradation rate of PGA is relatively fast, especially the strength decays rapidly in a short time. PGA is the first biodegradable polymer material applied to absorb surgical sutures. The metabolites of its degradation product glycolic acid can eventually be completely excreted from the body without causing harm to the human body. Some literatures show that after PGA sutures are left in the body for 2 weeks, the tensile strength can be reduced by half, and the body can reach a state of complete degradation and absorption in about 4 months. The PGA material prepared by glycolic acid has a molecular weight of more than 10,000 and can be used for surgical sutures. However, due to its high crystallinity (46%-50%), it has the disadvantages of difficult processing, low strength, and fast degradation rate, but it cannot meet the performance requirements of implantable materials. Therefore, people modify it through a variety of methods to optimize its physical and chemical properties to expand its application field. For example, through copolymerization modification to form a copolymer that integrates the properties of the two to improve the degradability, biocompatibility, mechanical properties of PGA, etc.; or implement blending modification to form a blend by adding its own polymer fibers or additives, etc. , To improve the strength and other properties of PGA. Currently, modified PGA has been widely used in absorbable sutures, tissue engineering, drug control systems, absorbable bone nails, bone plates, and surgical correction materials.
(2) Polylactic acid (PLA)
In 1966, Kulkarni et al. found that low-molecular-weight and high-molecular-weight PLA have excellent biocompatibility. The final degradation products are H2O and CO2. The intermediate product lactic acid is also a normal sugar metabolite in the body, which will not cause any adverse effects on the organism. This led to the research and application of PLA as a biomedical material [29-30]. In 1997, PLA was approved by the FDA for clinical use as pharmaceutical excipients and medical sutures. PLA is a homopolymer of lactic acid monomer. Because lactide (LA) is a chiral molecule, there are two kinds of optically active substances, so PLA also has L-polylactic acid (PLLA), right-handed polylactic acid (PDLA), racemization Polylactic acid (PDLLA) these three three-dimensional configurations. Among them, PLLA and PDLA are semi-crystalline polymers with high tensile strength and slow degradation rate. They are ideal materials for surgical plastic materials, surgical sutures and implant materials; while PDLLA is an amorphous copolymer with low strength and degradation rate. Fast, often used in drug delivery carriers and low-strength tissue regeneration scaffolds. However, PLA's degradation rate is difficult to control, brittle, and poor impact resistance, which severely limits its application range. In recent years, people have used different modification methods such as copolymerization modification, preparation of self-reinforced polylactic acid, or formation of composite materials with other substances to control the degradation rate and improve the flexibility of PLA, so as to continuously expand its application fields. For example, polylactic acid is a hydrophobic polymer, which limits its application in drug carriers. Therefore, people improve its hydrophilicity by copolymerizing polylactic acid with hydrophilic substances (such as polyethylene glycol, polyglycolic acid, polyethylene oxide, etc.). Currently, PLA/PLGA implants have been widely used as slow and controlled release carriers for anti-tumor drugs, polypeptides, protein drugs, and Chinese medicines. In addition, PLA and modified PLA are widely used in ophthalmic materials, surgical sutures, internal fixation materials for fractures, and tissue engineering repairs.
(3) Polycaprolactone (PCL)
PCL is a semi-crystalline linear polyester with low melting point and glass transition temperature, very low tensile strength (23 MPa), high elongation at break (700%), and is easily soluble in many organic solvents. Copolymerized with a variety of polymers, it has good thermoplasticity and molding processability; in addition, PCL raw materials are easily available, the degradation rate is slow, and it has excellent drug permeability and biocompatibility. Therefore, it is widely used as surgical sutures, internal bone graft fixation devices, medical equipment, and biodegradable controlled release carriers. In addition, by modifying PLA to improve its hydrophilicity and degradation rate, its application range can be further expanded, such as organ repair materials, artificial skin, surgical anti-adhesion membranes, and tissue and cell engineering.
3. Conclusion
Biodegradable materials show good physical and chemical properties, biological properties, and biomechanical properties, and can be adjusted and processed according to actual conditions, which meets the functional needs of biomedicine to the greatest extent, and makes them useful in many fields of biomedicine. Widely used, at this stage, the research hotspot of biodegradable materials in the field of biomedicine has begun to transfer from suture and fixation to more complex fields such as tissue engineering scaffold materials. However, in practical applications, the high cost of biodegradable materials still has a certain impact on their grassroots promotion. In particular, the problem of controlling the degradation rate suitable for different objects needs to be solved urgently. For example, how to adjust the degradation rate of PCL to meet the needs of short-term drug carriers, and how to adjust the degradation rate of PLA to meet the needs of bone tissue engineering. But in general, it is believed that with the continuous development and advancement of related disciplines and technologies, the problems related to the degradation rate control of biodegradable materials and material costs will be gradually solved. The research and development of biodegradable materials in the field of biomedicine The application will also be further developed.
1. Degradation principle of biodegradable materials
Biodegradable materials interact with the biological environment of various factors such as body fluids, organic macromolecules, enzymes, free radicals, cells, etc., and gradually degrade into low molecular weight compounds through a series of reactions such as hydrolysis, enzymolysis, and oxidation. monomer. After absorption, digestion, and metabolic reactions, the degradation products are excreted from the body or participate in the normal metabolism of the body to be absorbed by the body to complete the degradation process. If the body fluid enters the biological material from the tissue or a certain component of the biological material is dissolved in the body fluid, the material will expand due to the increase in volume and exudate its own substance. This process destroys the hydrogen bond and van der Waals force of the material itself. , Will cause cracks or voids in the material, and eventually the material will gradually undergo chemical degradation in the biological environment. In clinical practice, people hope that the implanted biodegradable materials will also complete the differentiation and degradation reactions during the biological tissue treatment period according to the same procedure, so as to avoid the body's inflammation or stress response due to the implanted materials. We know that the treatment time for skin tissue is usually within 3 to 10 days, the treatment time for visceral tissue is usually between 1 and 2 months, and the treatment time for large organ tissues often takes 6 months or more. After biodegradable biomaterials are implanted in the human body, their degradation performance and degradation products have a great impact on the biological environment, material reactions and human body reactions. The slow degradation rate or the long residence time of degradation products can easily cause inflammation in human tissues. , Thrombosis and other adverse reactions. Studies [6] have shown that the degradation process and progress of most biodegradable materials are inconsistent with the best expected results. Therefore, in the research and clinical application of biodegradable materials, the degradation-related issues of biodegradable materials must be treated with caution, especially the degradation rate and degradation products.
2. Basic classification and application of biodegradable materials
Biodegradable materials are used in the human body and must meet strict conditions in terms of the material itself and its effects on the human body: easy to process, low price, easy to sterilize, definite degradation time, biological stability and mechanical properties to meet the needs of the implantation site , Good histocompatibility, blood compatibility and mechanical compatibility, no pyrogen reaction, genetic toxicity, teratogenicity and carcinogenicity, no irritation and sensitization.
At present, biodegradable materials can be classified according to different processes and sources, including natural polymer degradable materials, microbial synthetic degradable polymer materials, and chemically synthesized degradable polymer materials [3,9]. The specific classification and application are summarized as follows:
1. Natural polymer biodegradable materials
Currently, the most commonly used natural polymer biodegradable materials in the biomedical field mainly include gelatin, collagen, polysaccharides, and silk fibroin.
(1) Gelatin material
Gelatin is mostly derived from mammalian skin, bone, tendon, tail and other tissues. Its most notable feature is water-soluble polymer, which slowly expands and softens after absorbing water, and has biocompatibility, gelation, and biodegradability. Utilizing the characteristics of gelatin, easy to form, degradable by enzymes, and easy to be absorbed by the human body, it can be used as a slow-release material in drug carriers, excipients or slow-release shells; because of its good air permeability and water permeability As a wound dressing and artificial skin material, it can prevent fluid from the wound or the occurrence of secondary infection symptoms; in addition, gelatin plasma substitutes are degradable, non-toxic and non-immunogenic, etc. Clinical advantage.
(2) Collagen
Collagen is the main component of connective tissue, which accounts for about 1/3 of the protein content in animals. It is mainly found in animal tissues, skin, ligaments and cartilage. It has the functions of supporting body organs, maintaining mechanical stability, elasticity and strength. As a natural biological resource, it has the characteristics of good biocompatibility, low immunogenicity and biodegradability; clinical use has shown that collagen can significantly promote the repair, regeneration and reconstruction of defective tissues; but it lacks sufficient The mechanical strength can be improved by cross-linking modification or composite use with other biological materials]. At present, collagen has been widely used in the preparation of biodegradable sutures, hemostatic agents and wound dressings, biological patches, bone repair materials, hemodialysis membranes, hemostatic agents, drug release carriers, and as tissue engineering scaffolds, various ophthalmic treatments Devices and other aspects. However, in view of the complexity of clinical issues and the need for product upgrades, there are still many problems to be solved in the application research of collagen, such as the potential immune response of heterologous collagen, the possible cytotoxicity of residual cross-linking agent, and implantation. The mechanical strength and degradation controllability of collagen-like products.
(3) Polysaccharide materials
Polysaccharide materials are mostly derived from starch, hyaluronic acid, heparin, chitin and other ingredients, and their biocompatibility and biodegradability are very ideal. In nature, chitin is rich in content and is a large class of important polysaccharides except cellulose. It is non-toxic and has no side effects. It has good affinity for human cells, does not cause rejection, and has good biocompatibility and Degradability. In addition, it also has the characteristics of antibacterial, antiviral, antitumor, promoting wound healing and strong adsorption capacity. Because chitin contains many polar groups such as hydrogen bonds and has high crystallinity, it is insoluble in acid and alkali, and insoluble in water, so it is difficult to be used by the body. However, chitin can be dissolved in dilute acid and body fluids after being deacetylated into chitosan, and can be used by the human body. Chitin and chitosan have high chemical reactivity, and their derivatives after amidation, carboxylation, cyanation, acidification and other modifications are widely used in the medical field, such as hemostatic agents, flocculants, absorbable surgical sutures , Artificial skin, wound dressings, slow-release agents of anti-cancer drugs or chemotherapeutics, immobilized enzyme carriers, separation membrane materials, etc.
(4) Silk fibroin
Silk fibroin is mostly derived from silk and contains very rich amino acids inside, so it has good biocompatibility, and has been proven to be non-allergenic or carcinogenic, with excellent transparency and air permeability, and good film-forming effect. However, due to the molecular structure of silk fibroin, the hydrophilicity of silk fibroin and the mechanical properties after film formation are not good. Through the blending modification method, the hydrogen bonds and other forces formed between the mixed macromolecules and silk fibroin are Inducing silk fibroin molecules to change the structure can effectively improve the mechanical properties, thermal properties and water solubility of silk fibroin materials. At present, in the field of biomedicine, it is widely used in wound coating materials, artificial skin, artificial tendon ligaments, contact lenses, drug carriers, artificial blood vessel carriers and other fields.
2. Microbial synthesis of degradable polymer materials
Microbial synthesis of degradable polymer materials refers to the use of certain organic matter (such as glucose or starch) as a food source to synthesize carbon source organic matter into a polyester with differentiable characteristics under a series of complex reactions such as the fermentation of micro organisms Or polysaccharide polymers. At present, microbial synthetic polymer biodegradable materials widely used in clinical practice mainly include two types: biopolyester (PHA) and polyhydroxybutyl ester (PHB). Take PHB as an example. PHB is a high molecular polymer synthesized by microbial cells. Its structure and performance are different from natural macromolecular degradable materials, but more similar to aliphatic polyester polymers, with natural and chemical synthesis degradable The advantage of polymer, the degradation products are finally excreted as carbon dioxide and water through metabolism, without any toxic substances that may be produced by the synthesis of chemical raw materials. In addition, Tang Suyang and other studies have shown that PHB has excellent biocompatibility. At present, it has been widely used in absorbable surgical sutures, orthopedic materials, and drug control systems.
3. Chemical synthesis of degradable polymer materials
Compared with natural polymers, biodegradable polymer materials synthesized by chemical methods can be selected according to the needs of actual applications, by selecting appropriate monomers, or by controlling the reaction conditions in the synthesis process, or performing simple and low-cost Physical or chemical modification, etc., to design and adjust its structure and performance to achieve the purpose of synthesizing the target material. For example, through chemical control methods, the strength, degradation rate, microporous structure and permeability of polymer materials can be improved to expand the application field. In the chemically synthesized biodegradable polymers currently developed and researched, the main chain generally contains hydrolyzable ester groups, amido groups or urea groups. The following is the most researched and most widely used type of chemically synthesized degradable polymer materials in the current clinical biomedical practice—aliphatic polyester materials, such as polyglycolide (PGA), polylactic acid (PLA), and polylactic acid -Glycolic acid copolymer (PLGA), polycaprolactone (PCL), etc. will be introduced.
(1) Polyglycolide (PGA)
PGA is the linear aliphatic polyester with the simplest structure. It uses glycolic acid as the basic source and has a wide range of raw materials, mainly sugar beet, immature grape juice and sugar cane. Among the existing biodegradable polymers, the degradation rate of PGA is relatively fast, especially the strength decays rapidly in a short time. PGA is the first biodegradable polymer material applied to absorb surgical sutures. The metabolites of its degradation product glycolic acid can eventually be completely excreted from the body without causing harm to the human body. Some literatures show that after PGA sutures are left in the body for 2 weeks, the tensile strength can be reduced by half, and the body can reach a state of complete degradation and absorption in about 4 months. The PGA material prepared by glycolic acid has a molecular weight of more than 10,000 and can be used for surgical sutures. However, due to its high crystallinity (46%-50%), it has the disadvantages of difficult processing, low strength, and fast degradation rate, but it cannot meet the performance requirements of implantable materials. Therefore, people modify it through a variety of methods to optimize its physical and chemical properties to expand its application field. For example, through copolymerization modification to form a copolymer that integrates the properties of the two to improve the degradability, biocompatibility, mechanical properties of PGA, etc.; or implement blending modification to form a blend by adding its own polymer fibers or additives, etc. , To improve the strength and other properties of PGA. Currently, modified PGA has been widely used in absorbable sutures, tissue engineering, drug control systems, absorbable bone nails, bone plates, and surgical correction materials.
(2) Polylactic acid (PLA)
In 1966, Kulkarni et al. found that low-molecular-weight and high-molecular-weight PLA have excellent biocompatibility. The final degradation products are H2O and CO2. The intermediate product lactic acid is also a normal sugar metabolite in the body, which will not cause any adverse effects on the organism. This led to the research and application of PLA as a biomedical material [29-30]. In 1997, PLA was approved by the FDA for clinical use as pharmaceutical excipients and medical sutures. PLA is a homopolymer of lactic acid monomer. Because lactide (LA) is a chiral molecule, there are two kinds of optically active substances, so PLA also has L-polylactic acid (PLLA), right-handed polylactic acid (PDLA), racemization Polylactic acid (PDLLA) these three three-dimensional configurations. Among them, PLLA and PDLA are semi-crystalline polymers with high tensile strength and slow degradation rate. They are ideal materials for surgical plastic materials, surgical sutures and implant materials; while PDLLA is an amorphous copolymer with low strength and degradation rate. Fast, often used in drug delivery carriers and low-strength tissue regeneration scaffolds. However, PLA's degradation rate is difficult to control, brittle, and poor impact resistance, which severely limits its application range. In recent years, people have used different modification methods such as copolymerization modification, preparation of self-reinforced polylactic acid, or formation of composite materials with other substances to control the degradation rate and improve the flexibility of PLA, so as to continuously expand its application fields. For example, polylactic acid is a hydrophobic polymer, which limits its application in drug carriers. Therefore, people improve its hydrophilicity by copolymerizing polylactic acid with hydrophilic substances (such as polyethylene glycol, polyglycolic acid, polyethylene oxide, etc.). Currently, PLA/PLGA implants have been widely used as slow and controlled release carriers for anti-tumor drugs, polypeptides, protein drugs, and Chinese medicines. In addition, PLA and modified PLA are widely used in ophthalmic materials, surgical sutures, internal fixation materials for fractures, and tissue engineering repairs.
(3) Polycaprolactone (PCL)
PCL is a semi-crystalline linear polyester with low melting point and glass transition temperature, very low tensile strength (23 MPa), high elongation at break (700%), and is easily soluble in many organic solvents. Copolymerized with a variety of polymers, it has good thermoplasticity and molding processability; in addition, PCL raw materials are easily available, the degradation rate is slow, and it has excellent drug permeability and biocompatibility. Therefore, it is widely used as surgical sutures, internal bone graft fixation devices, medical equipment, and biodegradable controlled release carriers. In addition, by modifying PLA to improve its hydrophilicity and degradation rate, its application range can be further expanded, such as organ repair materials, artificial skin, surgical anti-adhesion membranes, and tissue and cell engineering.
3. Conclusion
Biodegradable materials show good physical and chemical properties, biological properties, and biomechanical properties, and can be adjusted and processed according to actual conditions, which meets the functional needs of biomedicine to the greatest extent, and makes them useful in many fields of biomedicine. Widely used, at this stage, the research hotspot of biodegradable materials in the field of biomedicine has begun to transfer from suture and fixation to more complex fields such as tissue engineering scaffold materials. However, in practical applications, the high cost of biodegradable materials still has a certain impact on their grassroots promotion. In particular, the problem of controlling the degradation rate suitable for different objects needs to be solved urgently. For example, how to adjust the degradation rate of PCL to meet the needs of short-term drug carriers, and how to adjust the degradation rate of PLA to meet the needs of bone tissue engineering. But in general, it is believed that with the continuous development and advancement of related disciplines and technologies, the problems related to the degradation rate control of biodegradable materials and material costs will be gradually solved. The research and development of biodegradable materials in the field of biomedicine The application will also be further developed.
1. Degradation principle of biodegradable materials
Biodegradable materials interact with the biological environment of various factors such as body fluids, organic macromolecules, enzymes, free radicals, cells, etc., and gradually degrade into low molecular weight compounds through a series of reactions such as hydrolysis, enzymolysis, and oxidation. monomer. After absorption, digestion, and metabolic reactions, the degradation products are excreted from the body or participate in the normal metabolism of the body to be absorbed by the body to complete the degradation process. If the body fluid enters the biological material from the tissue or a certain component of the biological material is dissolved in the body fluid, the material will expand due to the increase in volume and exudate its own substance. This process destroys the hydrogen bond and van der Waals force of the material itself. , Will cause cracks or voids in the material, and eventually the material will gradually undergo chemical degradation in the biological environment. In clinical practice, people hope that the implanted biodegradable materials will also complete the differentiation and degradation reactions during the biological tissue treatment period according to the same procedure, so as to avoid the body's inflammation or stress response due to the implanted materials. We know that the treatment time for skin tissue is usually within 3 to 10 days, the treatment time for visceral tissue is usually between 1 and 2 months, and the treatment time for large organ tissues often takes 6 months or more. After biodegradable biomaterials are implanted in the human body, their degradation performance and degradation products have a great impact on the biological environment, material reactions and human body reactions. The slow degradation rate or the long residence time of degradation products can easily cause inflammation in human tissues. , Thrombosis and other adverse reactions. Studies [6] have shown that the degradation process and progress of most biodegradable materials are inconsistent with the best expected results. Therefore, in the research and clinical application of biodegradable materials, the degradation-related issues of biodegradable materials must be treated with caution, especially the degradation rate and degradation products.
2. Basic classification and application of biodegradable materials
Biodegradable materials are used in the human body and must meet strict conditions in terms of the material itself and its effects on the human body: easy to process, low price, easy to sterilize, definite degradation time, biological stability and mechanical properties to meet the needs of the implantation site , Good histocompatibility, blood compatibility and mechanical compatibility, no pyrogen reaction, genetic toxicity, teratogenicity and carcinogenicity, no irritation and sensitization.
At present, biodegradable materials can be classified according to different processes and sources, including natural polymer degradable materials, microbial synthetic degradable polymer materials, and chemically synthesized degradable polymer materials [3,9]. The specific classification and application are summarized as follows:
1. Natural polymer biodegradable materials
Currently, the most commonly used natural polymer biodegradable materials in the biomedical field mainly include gelatin, collagen, polysaccharides, and silk fibroin.
(1) Gelatin material
Gelatin is mostly derived from mammalian skin, bone, tendon, tail and other tissues. Its most notable feature is water-soluble polymer, which slowly expands and softens after absorbing water, and has biocompatibility, gelation, and biodegradability. Utilizing the characteristics of gelatin, easy to form, degradable by enzymes, and easy to be absorbed by the human body, it can be used as a slow-release material in drug carriers, excipients or slow-release shells; because of its good air permeability and water permeability As a wound dressing and artificial skin material, it can prevent fluid from the wound or the occurrence of secondary infection symptoms; in addition, gelatin plasma substitutes are degradable, non-toxic and non-immunogenic, etc. Clinical advantage.
(2) Collagen
Collagen is the main component of connective tissue, which accounts for about 1/3 of the protein content in animals. It is mainly found in animal tissues, skin, ligaments and cartilage. It has the functions of supporting body organs, maintaining mechanical stability, elasticity and strength. As a natural biological resource, it has the characteristics of good biocompatibility, low immunogenicity and biodegradability; clinical use has shown that collagen can significantly promote the repair, regeneration and reconstruction of defective tissues; but it lacks sufficient The mechanical strength can be improved by cross-linking modification or composite use with other biological materials]. At present, collagen has been widely used in the preparation of biodegradable sutures, hemostatic agents and wound dressings, biological patches, bone repair materials, hemodialysis membranes, hemostatic agents, drug release carriers, and as tissue engineering scaffolds, various ophthalmic treatments Devices and other aspects. However, in view of the complexity of clinical issues and the need for product upgrades, there are still many problems to be solved in the application research of collagen, such as the potential immune response of heterologous collagen, the possible cytotoxicity of residual cross-linking agent, and implantation. The mechanical strength and degradation controllability of collagen-like products.
(3) Polysaccharide materials
Polysaccharide materials are mostly derived from starch, hyaluronic acid, heparin, chitin and other ingredients, and their biocompatibility and biodegradability are very ideal. In nature, chitin is rich in content and is a large class of important polysaccharides except cellulose. It is non-toxic and has no side effects. It has good affinity for human cells, does not cause rejection, and has good biocompatibility and Degradability. In addition, it also has the characteristics of antibacterial, antiviral, antitumor, promoting wound healing and strong adsorption capacity. Because chitin contains many polar groups such as hydrogen bonds and has high crystallinity, it is insoluble in acid and alkali, and insoluble in water, so it is difficult to be used by the body. However, chitin can be dissolved in dilute acid and body fluids after being deacetylated into chitosan, and can be used by the human body. Chitin and chitosan have high chemical reactivity, and their derivatives after amidation, carboxylation, cyanation, acidification and other modifications are widely used in the medical field, such as hemostatic agents, flocculants, absorbable surgical sutures , Artificial skin, wound dressings, slow-release agents of anti-cancer drugs or chemotherapeutics, immobilized enzyme carriers, separation membrane materials, etc.
(4) Silk fibroin
Silk fibroin is mostly derived from silk and contains very rich amino acids inside, so it has good biocompatibility, and has been proven to be non-allergenic or carcinogenic, with excellent transparency and air permeability, and good film-forming effect. However, due to the molecular structure of silk fibroin, the hydrophilicity of silk fibroin and the mechanical properties after film formation are not good. Through the blending modification method, the hydrogen bonds and other forces formed between the mixed macromolecules and silk fibroin are Inducing silk fibroin molecules to change the structure can effectively improve the mechanical properties, thermal properties and water solubility of silk fibroin materials. At present, in the field of biomedicine, it is widely used in wound coating materials, artificial skin, artificial tendon ligaments, contact lenses, drug carriers, artificial blood vessel carriers and other fields.
2. Microbial synthesis of degradable polymer materials
Microbial synthesis of degradable polymer materials refers to the use of certain organic matter (such as glucose or starch) as a food source to synthesize carbon source organic matter into a polyester with differentiable characteristics under a series of complex reactions such as the fermentation of micro organisms Or polysaccharide polymers. At present, microbial synthetic polymer biodegradable materials widely used in clinical practice mainly include two types: biopolyester (PHA) and polyhydroxybutyl ester (PHB). Take PHB as an example. PHB is a high molecular polymer synthesized by microbial cells. Its structure and performance are different from natural macromolecular degradable materials, but more similar to aliphatic polyester polymers, with natural and chemical synthesis degradable The advantage of polymer, the degradation products are finally excreted as carbon dioxide and water through metabolism, without any toxic substances that may be produced by the synthesis of chemical raw materials. In addition, Tang Suyang and other studies have shown that PHB has excellent biocompatibility. At present, it has been widely used in absorbable surgical sutures, orthopedic materials, and drug control systems.
3. Chemical synthesis of degradable polymer materials
Compared with natural polymers, biodegradable polymer materials synthesized by chemical methods can be selected according to the needs of actual applications, by selecting appropriate monomers, or by controlling the reaction conditions in the synthesis process, or performing simple and low-cost Physical or chemical modification, etc., to design and adjust its structure and performance to achieve the purpose of synthesizing the target material. For example, through chemical control methods, the strength, degradation rate, microporous structure and permeability of polymer materials can be improved to expand the application field. In the chemically synthesized biodegradable polymers currently developed and researched, the main chain generally contains hydrolyzable ester groups, amido groups or urea groups. The following is the most researched and most widely used type of chemically synthesized degradable polymer materials in the current clinical biomedical practice—aliphatic polyester materials, such as polyglycolide (PGA), polylactic acid (PLA), and polylactic acid -Glycolic acid copolymer (PLGA), polycaprolactone (PCL), etc. will be introduced.
(1) Polyglycolide (PGA)
PGA is the linear aliphatic polyester with the simplest structure. It uses glycolic acid as the basic source and has a wide range of raw materials, mainly sugar beet, immature grape juice and sugar cane. Among the existing biodegradable polymers, the degradation rate of PGA is relatively fast, especially the strength decays rapidly in a short time. PGA is the first biodegradable polymer material applied to absorb surgical sutures. The metabolites of its degradation product glycolic acid can eventually be completely excreted from the body without causing harm to the human body. Some literatures show that after PGA sutures are left in the body for 2 weeks, the tensile strength can be reduced by half, and the body can reach a state of complete degradation and absorption in about 4 months. The PGA material prepared by glycolic acid has a molecular weight of more than 10,000 and can be used for surgical sutures. However, due to its high crystallinity (46%-50%), it has the disadvantages of difficult processing, low strength, and fast degradation rate, but it cannot meet the performance requirements of implantable materials. Therefore, people modify it through a variety of methods to optimize its physical and chemical properties to expand its application field. For example, through copolymerization modification to form a copolymer that integrates the properties of the two to improve the degradability, biocompatibility, mechanical properties of PGA, etc.; or implement blending modification to form a blend by adding its own polymer fibers or additives, etc. , To improve the strength and other properties of PGA. Currently, modified PGA has been widely used in absorbable sutures, tissue engineering, drug control systems, absorbable bone nails, bone plates, and surgical correction materials.
(2) Polylactic acid (PLA)
In 1966, Kulkarni et al. found that low-molecular-weight and high-molecular-weight PLA have excellent biocompatibility. The final degradation products are H2O and CO2. The intermediate product lactic acid is also a normal sugar metabolite in the body, which will not cause any adverse effects on the organism. This led to the research and application of PLA as a biomedical material [29-30]. In 1997, PLA was approved by the FDA for clinical use as pharmaceutical excipients and medical sutures. PLA is a homopolymer of lactic acid monomer. Because lactide (LA) is a chiral molecule, there are two kinds of optically active substances, so PLA also has L-polylactic acid (PLLA), right-handed polylactic acid (PDLA), racemization Polylactic acid (PDLLA) these three three-dimensional configurations. Among them, PLLA and PDLA are semi-crystalline polymers with high tensile strength and slow degradation rate. They are ideal materials for surgical plastic materials, surgical sutures and implant materials; while PDLLA is an amorphous copolymer with low strength and degradation rate. Fast, often used in drug delivery carriers and low-strength tissue regeneration scaffolds. However, PLA's degradation rate is difficult to control, brittle, and poor impact resistance, which severely limits its application range. In recent years, people have used different modification methods such as copolymerization modification, preparation of self-reinforced polylactic acid, or formation of composite materials with other substances to control the degradation rate and improve the flexibility of PLA, so as to continuously expand its application fields. For example, polylactic acid is a hydrophobic polymer, which limits its application in drug carriers. Therefore, people improve its hydrophilicity by copolymerizing polylactic acid with hydrophilic substances (such as polyethylene glycol, polyglycolic acid, polyethylene oxide, etc.). Currently, PLA/PLGA implants have been widely used as slow and controlled release carriers for anti-tumor drugs, polypeptides, protein drugs, and Chinese medicines. In addition, PLA and modified PLA are widely used in ophthalmic materials, surgical sutures, internal fixation materials for fractures, and tissue engineering repairs.
(3) Polycaprolactone (PCL)
PCL is a semi-crystalline linear polyester with low melting point and glass transition temperature, very low tensile strength (23 MPa), high elongation at break (700%), and is easily soluble in many organic solvents. Copolymerized with a variety of polymers, it has good thermoplasticity and molding processability; in addition, PCL raw materials are easily available, the degradation rate is slow, and it has excellent drug permeability and biocompatibility. Therefore, it is widely used as surgical sutures, internal bone graft fixation devices, medical equipment, and biodegradable controlled release carriers. In addition, by modifying PLA to improve its hydrophilicity and degradation rate, its application range can be further expanded, such as organ repair materials, artificial skin, surgical anti-adhesion membranes, and tissue and cell engineering.
3. Conclusion
Biodegradable materials show good physical and chemical properties, biological properties, and biomechanical properties, and can be adjusted and processed according to actual conditions, which meets the functional needs of biomedicine to the greatest extent, and makes them useful in many fields of biomedicine. Widely used, at this stage, the research hotspot of biodegradable materials in the field of biomedicine has begun to transfer from suture and fixation to more complex fields such as tissue engineering scaffold materials. However, in practical applications, the high cost of biodegradable materials still has a certain impact on their grassroots promotion. In particular, the problem of controlling the degradation rate suitable for different objects needs to be solved urgently. For example, how to adjust the degradation rate of PCL to meet the needs of short-term drug carriers, and how to adjust the degradation rate of PLA to meet the needs of bone tissue engineering. But in general, it is believed that with the continuous development and advancement of related disciplines and technologies, the problems related to the degradation rate control of biodegradable materials and material costs will be gradually solved. The research and development of biodegradable materials in the field of biomedicine The application will also be further developed.
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