CA2699129A1 - Biological artificial ligament and preparation method thereof - Google Patents
Biological artificial ligament and preparation method thereof Download PDFInfo
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- CA2699129A1 CA2699129A1 CA2699129A CA2699129A CA2699129A1 CA 2699129 A1 CA2699129 A1 CA 2699129A1 CA 2699129 A CA2699129 A CA 2699129A CA 2699129 A CA2699129 A CA 2699129A CA 2699129 A1 CA2699129 A1 CA 2699129A1
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- Prior art keywords
- ligament
- compound
- tendon
- reagent
- hydrogen bonding
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
- A61L27/3645—Connective tissue
- A61L27/3662—Ligaments, tendons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
Abstract
A biological artificial ligament having a fresh animal ligament or tendon as a substrate, and the substrate is pretreated with a sterilant and defatted, a specific active group in protein molecules of the ligament or tendon is blocked with an active reagent, a specific hydrogen bonding in the spiral chains of the protein molecules is replaced with a reagent with strong hydrogen bonding power, the protein molecule in the animal ligament or tendon is crosslinked with an epoxy compound, an acetyl diamide compound, a diisocyanate, or a carbodiimide, and an active layer having either a polypeptide or a glucosaminoglycan with capacity of adhering growth factors is coupled to the surface of the animal ligament or tendon by a coupling agent. A method of preparation of a biological artificial ligament is also provided.
Description
BIOLOGICAL ARTIFICIAL LIGAMENT AND PREPARATION METHOD
THEREOF
FIELD OF THE INVENTION
[0001 ] The invention relates to a biological artificial ligament for rebuilding a torn ligament of a patient and a preparation method thereof.
BACKGROUND OF THE INVENTION
THEREOF
FIELD OF THE INVENTION
[0001 ] The invention relates to a biological artificial ligament for rebuilding a torn ligament of a patient and a preparation method thereof.
BACKGROUND OF THE INVENTION
[0002] A torn ligament is one of the most common sport injuries and easily causes joint instability and cartilage degeneration. Treatment for such a disease mainly focuses on autologous transplant, allogenic transplant, or artificial ligament. However, either autologous transplant or allogenic transplant has disadvantages such as severe complications and immune reaction, and the source is very limited. Artificial ligament arouses more attention due to rich source and short recovery time.
[0003] Conventional artificial ligaments are mainly composed of polymeric substances synthesized with polyester, nylons, or polytetrafluoroethylene, etc. These synthetic polymers are different from body tissues with respect to their composition and structure, so the risk of aseptic inflammation and inherent creep deformation is ever present.
[0004] In recent years, bovine tendons are attempted to prepare artificial tendons and ligaments with glutaraldehyde as crosslinking agent and fixative. However, the method is not involved in removing antigens, and glutaraldehyde is poisonous, not stable, and tended to be released with the degradation of artificial ligaments.
SUMMARY OF INVENTION
SUMMARY OF INVENTION
[0005] In view of the above described problems, it is one objective of the invention to provide a safe and reliable biological artificial ligament having high biocompatibility, stability, and resistance to degradation.
i [0006] It is another object of the invention to provide a method of preparing such an artificial ligament.
i [0006] It is another object of the invention to provide a method of preparing such an artificial ligament.
[0007] To achieve the above objectives, in accordance with one embodiment of the invention, there is provided a biological artificial ligament comprises a fresh animal ligament or tendon, wherein the ligament or tendon is pretreated with a sterilant and defatted, a specific active group in protein molecules of the ligament or tendon is blocked with an active reagent, a specific hydrogen bonding in the spiral chains of the protein molecules is replaced with a reagent with strong hydrogen bonding power, the protein molecule in the animal ligament or tendon is crosslinked with an epoxy compound, an acetyl diamide compound, a diisocyanate, or a carbodiimide, and an active layer having either a polypeptide or a glucosaminoglycan with capacity of adhering growth factors is coupled to the surface of the animal ligament or tendon by a coupling agent.
[0008] In accordance with another embodiment of the invention, there is provided a method of preparation of a biological artificial ligament, comprising the steps of:
[0009] 1) Collecting a fresh animal ligament or tendon as a substrate;
[0010] 2) Sterilizing the substrate;
[0011] 3) Defatting the substrate;
[0012] 4) Blocking a specific active group in protein molecules of the substrate with an active reagent;
[0013] 5) Replacing a specific hydrogen bonding in the spiral chains of the protein molecules with a reagent with strong hydrogen bonding power;
[0014] 6) Crosslinking the protein molecule with an epoxy compound, an acetyl diamide compound, a diisocyanate, or a carbodiimide; and [0015] 7) Coupling an active layer having either a polypeptide or a glucosaminoglycan with capacity of adhering growth factors to the surface of the substrate by a coupling agent.
[0016] In a class of this embodiment, the steri lant is selected from benzalkonium bromide, sodium azide, or chlorhexidine.
[0017] In a class of this embodiment, the active reagent is acid anhydride, acid chloride, acylamide, or a monoepoxy compound.
[0018] In a class of this embodiment, the reagent with strong hydrogen bonding power is a guanidine compound.
[00 19] In a class of this embodiment, the polypeptide consists of 16 lysine (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P), and cysteine (C).
[0020] In a class of this embodiment, the glucosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, acetylated heparin sulfate, or keratin sulfate.
[0021 ] In a class of this embodiment, the coupling agent is an acetyl diamide compound, or a dioic anhydride compound, or a diepoxy compound, or other compounds with double functional groups which participate in a condensation reaction with groups of -NH2, -OH, or -COOH. In a class of this embodiment, the epoxy compound is a monoepoxy compound having a formula of R "*__N7 0 , or a diepoxy compound having a formula of 0 0 , or an oligoepoxy compound, such as polypropylene oxide; and R =
-C,H2n+I, and n= 0-10.
[0022] Animal ligament or tendon tissues are easily degraded or decomposed by microorganisms, so that crosslinking and fixation with a fixative is required.
Conventionally, glutaraldehyde is utilized as a fixative, but glutaraldehyde produces toxic radicals. However, aldehydes undergo crosslinking with proteins through the acetal reaction and toxic aldehydes are released when the crosslinked products are degraded, so that products fixed with an aldehyde have long-term residual toxicity. When epoxides, diamides, diisocyanates or carbodiimides are utilized as fixatives in place of aldehydes, the toxicity problem is eliminated. When an epoxide is utilized, for example, proteins are crosslinked through a ring opening reaction of the epoxide, and reverse ring closure to form the epoxide back does not readily occur, and the degradation products are diols and polyols which can be metabolized by the body so that there is no risk of toxic aldehyde radicals. The stability of the animal ligaments after treatment is also higher than those fixed with aldehydes.
[0023] According to modern immunological theory, the antigenicity of animal tissues stems mainly from active groups located at specific sites and in specific conformations, and these active groups include -OH, -NH2, -SH, etc. The specific conformations result mainly from some specific hydrogen bonding formed by spiral protein chains.
The specific sites and conformations are called antigen determinants. When treating the animal ligaments, one or several small, active reagents (e.g., acid anhydrides, acid chlorides, acylamides, epoxides, etc.) which can readily react with these groups are used to bind to and block these groups, which in turn effectively minimizes the antigenicity, and in the meantime strong hydrogen bonding reagents (e.g., guanidine compounds) are utilized to form new hydrogen bonds and replace the inherent hydrogen bonding of the specific conformations, which changes the specific conformations and further effectively minimizes the antigenicity. The structure of the animal ligaments cannot be easily altered after they have been crosslinked and fixed by non-aldehyde fixatives such as epoxides, and the tissues are not easily degraded or decomposed, and collagenase only begins to phagocytize and degrade them due to the synergistic effect of fibrinolysin and kallikrein released by nascent tissues, which means that the new ligament tissues have sufficient time to grow and take hold, while no toxic radicals remain. The immunogenicity is effectively minimized by blocking the active groups in the proteins and changing the conformation, and the resulting substrate has no chronic immune rejection while having excellent biocompatibility.
[0024] Furthermore, the tissue compatibility is improved by modifying the surface by incorporating an active component, including a specific polypeptide and glucosaminoglycan. The specific polypeptide and glucosaminoglycan have broad spectrum adhesion and affinity for growth factors, or are capable of activating undifferentiated cells to undergo oriented differentiation, which promotes regeneration and repairs the organic ligaments.
[0025] Advantages of the invention are summarized below:
[0026] 1) The biocompatibility is excellent without immune rejection, and the composition resembles that of human ligaments while the degradation products can be absorbed and utilized by new ligament tissues.
[0027] 2) The stability is high and it is not easily degraded under normal conditions, and collagenase only begins to phagocytize and degrade it under the synergistic effect of fibrinolysin and kallikrein released by nascent tissues, resulting in synchronized tissue degradation and regeneration.
[0028] 3) The mechanical strength is strong enough to completely satisfy the mechanical requirements for a ligament.
[0029] 4) An active component such as specific polypeptide or glucosaminoglycan is incorporated to modify the surface activity through coupling, so that growth factors can actively adhere to, and accumulate and activate undifferentiated cells to undergo oriented differentiation and improve the regenerative ability of the ligament, making it an excellent support and carrier for ligament repair. This characteristic is significantly better than the artificial ligaments of synthetic materials.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] The invention is described hereinbelow with reference to accompanying drawings, in which:
[0031] FIG. 1 is a perspective view of a biological artificial ligament according to one embodiment of the invention.
[0032] FIG. 2 is a cross-sectional view of the biological artificial ligament of FIG. 1.
[0033] Legends: 1. Substrate; 2. Active Layer DETAILED DESCRIPTION OF THE EMBODIMENTS
[0034] For further illustrating the invention, experiments detailing a biological artificial ligament and a method of the preparation of the biological artificial ligament are described below. It should be noted that the following examples are intended to describe and not to limit the invention.
[0035] Example 1 [0036] As shown in FIGS. 1 and 2, a biological artificial ligament comprising a substrate 1 was formed with an animal ligament or tendon crosslinked and fixed with an epoxide and treated to minimize antigens. An activated surface layer 2 was formed on the surface of the substrate 1 by coupling a specific polypeptide capable of adhering to and accumulating growth factors. In this example, the polypeptide was the polypeptide consisting of 16 lysine (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P) and cysteine (C), and the glucosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, acetylated heparin sulfate or keratin sulfate.
[0037] This biological artificial ligament was made through the following steps:
[0038] 1) Screening of materials: Fresh animal ligaments and tendons were collected by professional technicians from regulated and well-managed slaughterhouses while special efforts are made to avoid direct contact with pollutants.
[0039] 2) Pretreatment: Initial sterilization was performed using broad spectrum, highly-effective and low-toxicity bacteriacides such as benzalkonium bromide, sodium azide and chlorhexidine, followed by eliminating impurities and trimming irregular portions.
[0040] 3) Defatting: The fatty substances in the substrate 1 were extracted with organic solvents such as chloroform, acetone, ethyl acetate, diethyl ether, anhydrous alcohol or mixtures thereof.
[0041] 4) Minimizing antigens: The specific and active groups, -OH or -NH2 or -SH, of the proteins in the substrate 1 were blocked using low molecular weight, active reagents such as organic acid anhydrides, acyl chlorides, acylamides or monocyclic epoxides, and the specific hydrogen bonding on the spiral chains of the protein molecules of the substrate 1 was replaced using a strong hydrogen bonding reagent such as a guanidine compound, which alters the specific conformation of the proteins.
[0042] 5) Fixation: The protein molecules in the substrate 1 were crosslinked and fixed using a bicyclic oligoepoxide of the following formula as a fixative, where n = 0-10.
[0043] 6) Surface modification: An active ingredient such as a specific polypeptide was deposited on the surface of the substrate 1 through coupling using a diamide, acid anhydride, epoxide or other bifunctional reagent capable of undergoing condensation with -NH2, -OH, -COOH, etc., to form active surface layer 2 on the surface of the substrate 1.
[00 19] In a class of this embodiment, the polypeptide consists of 16 lysine (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P), and cysteine (C).
[0020] In a class of this embodiment, the glucosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, acetylated heparin sulfate, or keratin sulfate.
[0021 ] In a class of this embodiment, the coupling agent is an acetyl diamide compound, or a dioic anhydride compound, or a diepoxy compound, or other compounds with double functional groups which participate in a condensation reaction with groups of -NH2, -OH, or -COOH. In a class of this embodiment, the epoxy compound is a monoepoxy compound having a formula of R "*__N7 0 , or a diepoxy compound having a formula of 0 0 , or an oligoepoxy compound, such as polypropylene oxide; and R =
-C,H2n+I, and n= 0-10.
[0022] Animal ligament or tendon tissues are easily degraded or decomposed by microorganisms, so that crosslinking and fixation with a fixative is required.
Conventionally, glutaraldehyde is utilized as a fixative, but glutaraldehyde produces toxic radicals. However, aldehydes undergo crosslinking with proteins through the acetal reaction and toxic aldehydes are released when the crosslinked products are degraded, so that products fixed with an aldehyde have long-term residual toxicity. When epoxides, diamides, diisocyanates or carbodiimides are utilized as fixatives in place of aldehydes, the toxicity problem is eliminated. When an epoxide is utilized, for example, proteins are crosslinked through a ring opening reaction of the epoxide, and reverse ring closure to form the epoxide back does not readily occur, and the degradation products are diols and polyols which can be metabolized by the body so that there is no risk of toxic aldehyde radicals. The stability of the animal ligaments after treatment is also higher than those fixed with aldehydes.
[0023] According to modern immunological theory, the antigenicity of animal tissues stems mainly from active groups located at specific sites and in specific conformations, and these active groups include -OH, -NH2, -SH, etc. The specific conformations result mainly from some specific hydrogen bonding formed by spiral protein chains.
The specific sites and conformations are called antigen determinants. When treating the animal ligaments, one or several small, active reagents (e.g., acid anhydrides, acid chlorides, acylamides, epoxides, etc.) which can readily react with these groups are used to bind to and block these groups, which in turn effectively minimizes the antigenicity, and in the meantime strong hydrogen bonding reagents (e.g., guanidine compounds) are utilized to form new hydrogen bonds and replace the inherent hydrogen bonding of the specific conformations, which changes the specific conformations and further effectively minimizes the antigenicity. The structure of the animal ligaments cannot be easily altered after they have been crosslinked and fixed by non-aldehyde fixatives such as epoxides, and the tissues are not easily degraded or decomposed, and collagenase only begins to phagocytize and degrade them due to the synergistic effect of fibrinolysin and kallikrein released by nascent tissues, which means that the new ligament tissues have sufficient time to grow and take hold, while no toxic radicals remain. The immunogenicity is effectively minimized by blocking the active groups in the proteins and changing the conformation, and the resulting substrate has no chronic immune rejection while having excellent biocompatibility.
[0024] Furthermore, the tissue compatibility is improved by modifying the surface by incorporating an active component, including a specific polypeptide and glucosaminoglycan. The specific polypeptide and glucosaminoglycan have broad spectrum adhesion and affinity for growth factors, or are capable of activating undifferentiated cells to undergo oriented differentiation, which promotes regeneration and repairs the organic ligaments.
[0025] Advantages of the invention are summarized below:
[0026] 1) The biocompatibility is excellent without immune rejection, and the composition resembles that of human ligaments while the degradation products can be absorbed and utilized by new ligament tissues.
[0027] 2) The stability is high and it is not easily degraded under normal conditions, and collagenase only begins to phagocytize and degrade it under the synergistic effect of fibrinolysin and kallikrein released by nascent tissues, resulting in synchronized tissue degradation and regeneration.
[0028] 3) The mechanical strength is strong enough to completely satisfy the mechanical requirements for a ligament.
[0029] 4) An active component such as specific polypeptide or glucosaminoglycan is incorporated to modify the surface activity through coupling, so that growth factors can actively adhere to, and accumulate and activate undifferentiated cells to undergo oriented differentiation and improve the regenerative ability of the ligament, making it an excellent support and carrier for ligament repair. This characteristic is significantly better than the artificial ligaments of synthetic materials.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] The invention is described hereinbelow with reference to accompanying drawings, in which:
[0031] FIG. 1 is a perspective view of a biological artificial ligament according to one embodiment of the invention.
[0032] FIG. 2 is a cross-sectional view of the biological artificial ligament of FIG. 1.
[0033] Legends: 1. Substrate; 2. Active Layer DETAILED DESCRIPTION OF THE EMBODIMENTS
[0034] For further illustrating the invention, experiments detailing a biological artificial ligament and a method of the preparation of the biological artificial ligament are described below. It should be noted that the following examples are intended to describe and not to limit the invention.
[0035] Example 1 [0036] As shown in FIGS. 1 and 2, a biological artificial ligament comprising a substrate 1 was formed with an animal ligament or tendon crosslinked and fixed with an epoxide and treated to minimize antigens. An activated surface layer 2 was formed on the surface of the substrate 1 by coupling a specific polypeptide capable of adhering to and accumulating growth factors. In this example, the polypeptide was the polypeptide consisting of 16 lysine (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P) and cysteine (C), and the glucosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, acetylated heparin sulfate or keratin sulfate.
[0037] This biological artificial ligament was made through the following steps:
[0038] 1) Screening of materials: Fresh animal ligaments and tendons were collected by professional technicians from regulated and well-managed slaughterhouses while special efforts are made to avoid direct contact with pollutants.
[0039] 2) Pretreatment: Initial sterilization was performed using broad spectrum, highly-effective and low-toxicity bacteriacides such as benzalkonium bromide, sodium azide and chlorhexidine, followed by eliminating impurities and trimming irregular portions.
[0040] 3) Defatting: The fatty substances in the substrate 1 were extracted with organic solvents such as chloroform, acetone, ethyl acetate, diethyl ether, anhydrous alcohol or mixtures thereof.
[0041] 4) Minimizing antigens: The specific and active groups, -OH or -NH2 or -SH, of the proteins in the substrate 1 were blocked using low molecular weight, active reagents such as organic acid anhydrides, acyl chlorides, acylamides or monocyclic epoxides, and the specific hydrogen bonding on the spiral chains of the protein molecules of the substrate 1 was replaced using a strong hydrogen bonding reagent such as a guanidine compound, which alters the specific conformation of the proteins.
[0042] 5) Fixation: The protein molecules in the substrate 1 were crosslinked and fixed using a bicyclic oligoepoxide of the following formula as a fixative, where n = 0-10.
[0043] 6) Surface modification: An active ingredient such as a specific polypeptide was deposited on the surface of the substrate 1 through coupling using a diamide, acid anhydride, epoxide or other bifunctional reagent capable of undergoing condensation with -NH2, -OH, -COOH, etc., to form active surface layer 2 on the surface of the substrate 1.
Claims (12)
1. A biological artificial ligament comprises a fresh animal ligament or tendon, wherein said ligament or tendon is pretreated with a sterilant and defatted, a specific active group in protein molecules of said ligament or tendon is blocked with an active reagent, a specific hydrogen bonding in the spiral chains of the protein molecules is replaced with a reagent with strong hydrogen bonding power, the protein molecule in the animal ligament or tendon is crosslinked with an epoxy compound, an acetyl diamide compound, a diisocyanate, or a carbodiimide, and an active layer having either a polypeptide or a glucosaminoglycan with capacity of adhering growth factors is coupled to the surface of said animal ligament or tendon by a coupling agent.
2. The biological artificial ligament of claim 1, wherein said active reagent is acid anhydride, acid chloride, acylamide, or a monoepoxy compound.
3. The biological artificial ligament of claim 1 or 2, wherein said reagent with strong hydrogen bonding power is a guanidine compound.
4. The biological artificial ligament of claim 3, wherein said polypeptide consists of 16 lysine (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P), and cysteine (C).
5. The biological artificial ligament of claim 1, wherein said glucosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, acetylated heparin sulfate, or keratin sulfate.
6. The biological artificial ligament of claim 1, wherein said coupling agent is an acetyl diamide compound, or a dioic anhydride compound, or a diepoxy compound, or other compounds with double functional groups which participate in a condensation reaction with groups of -NH2, -OH, or -COOH.
7. A method of preparation of a biological artificial ligament, comprising the steps of:
1) Collecting a fresh animal ligament or tendon as a substrate;
2) Sterilizing said substrate;
3) Defatting said substrate;
4) Blocking a specific active group in protein molecules of said substrate with an active reagent;
5) Replacing a specific hydrogen bonding in the spiral chains of the protein molecules with a reagent with strong hydrogen bonding power;
6) Crosslinking the protein molecule with an epoxy compound, an acetyl diamide compound, a diisocyanate, or a carbodiimide; and 7) Coupling an active layer having either a polypeptide or a glucosaminoglycan with capacity of adhering growth factors to the surface of said substrate by a coupling agent.
1) Collecting a fresh animal ligament or tendon as a substrate;
2) Sterilizing said substrate;
3) Defatting said substrate;
4) Blocking a specific active group in protein molecules of said substrate with an active reagent;
5) Replacing a specific hydrogen bonding in the spiral chains of the protein molecules with a reagent with strong hydrogen bonding power;
6) Crosslinking the protein molecule with an epoxy compound, an acetyl diamide compound, a diisocyanate, or a carbodiimide; and 7) Coupling an active layer having either a polypeptide or a glucosaminoglycan with capacity of adhering growth factors to the surface of said substrate by a coupling agent.
8. The method of claim 7, wherein said active reagent is acid anhydride, acid chloride, acylamide, or a monoepoxy compound.
9. The method of claim 7 or 8, wherein said reagent with strong hydrogen bonding power is a guanidine compound.
10. The method of claim 9, wherein said polypeptide consists of 16 lysines (K16), glycine (G), arginine (R), aspartic acid (D), serine (S), proline (P), and cysteine (C).
11. The method of claim 7, wherein said glucosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparin, acetylated heparin sulfate, or keratin sulfate.
12. The method of claim 7, wherein said coupling agent is an acetyl diamide compound, or a dioic anhydride compound, or a diepoxy compound, or other compounds with double functional groups which participate in a condensation reaction with groups of -NH2, -OH, or -COOH.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2699129A CA2699129A1 (en) | 2010-04-07 | 2010-04-07 | Biological artificial ligament and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2699129A CA2699129A1 (en) | 2010-04-07 | 2010-04-07 | Biological artificial ligament and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2699129A1 true CA2699129A1 (en) | 2011-10-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2699129A Abandoned CA2699129A1 (en) | 2010-04-07 | 2010-04-07 | Biological artificial ligament and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116440328A (en) * | 2022-01-14 | 2023-07-18 | 爱美客技术发展股份有限公司 | Regulation method of degradation period of acellular biological tissue material and application thereof |
-
2010
- 2010-04-07 CA CA2699129A patent/CA2699129A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116440328A (en) * | 2022-01-14 | 2023-07-18 | 爱美客技术发展股份有限公司 | Regulation method of degradation period of acellular biological tissue material and application thereof |
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