WO2024013571A1 - Processing of human hyaline cartilage - Google Patents
Processing of human hyaline cartilage Download PDFInfo
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- WO2024013571A1 WO2024013571A1 PCT/IB2023/050992 IB2023050992W WO2024013571A1 WO 2024013571 A1 WO2024013571 A1 WO 2024013571A1 IB 2023050992 W IB2023050992 W IB 2023050992W WO 2024013571 A1 WO2024013571 A1 WO 2024013571A1
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Classifications
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Definitions
- Allograft cartilage is taken from donated human cartilage tissue.
- the advantage of an allogeneic cartilage graft is that not only does it fill the defect but also resists infection and is similar to an autogenous cartilage graft.
- the absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft.
- allograft cartilage was used in patients who did not have enough cartilage to use, or there were no suitable conditions for preparing their cartilage, for example, patients who did not agree to remove cartilage from the rib or ear, or due to previous cystoplasty, the patient did not have enough septal cartilage.
- the present disclosure provides tissue supports and methods for preparing a cartilage composition for repairing cartilage defects, which is prepared by expanding and integrating small cartilage tissue pieces derived from a donor or engineered tissue.
- the methods and supports described herein promote cell migration and integration of neighboring tissue pieces in culture to form the cartilage composition. Methods of cartilage repair using the cartilage composition are also described.
- the invention provides a composition including isolated small living tissue particles, a method of making the tissue particles, and a method of using the composition to ameliorate a tissue defect.
- the tissue particles are composed of cells and their associated extracellular molecules and are sized, in certain embodiments, to be smaller than about 1 mm. Another aspect of the inventive tissue particles is the large percentage of viable cells.
- the tissue particles are made from cartilage and the composition may also contain additives such as adhesives, solutions, and bioactive agents.
- a method for repairing cartilage tissues includes the following steps: adhering a plurality of endothelial progenitor cells onto a scaffold to form a composition and implanting the composition into an individual.
- the present invention also provides a method of cartilage defect treatment and a method for proliferating cartilage tissues.
- the methods in accordance with the present invention are advantageous for safely and quickly repairing or proliferating cartilage tissues for disease treatment and physical function maintenance.
- compositions and methods related to promoting the protection or repair of articular cartilage and/or musculoskeletal soft tissue by contacting the cartilage, tissues, or cellular components thereof with a parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor agonist or releasing factor.
- PTH/PTHrP parathyroid hormone/parathyroid hormone-related protein
- cartilage grafts plays an important role in plastic and reconstructive surgery, and the human body has limited resources for cartilage harvesting. Therefore, allograft cartilage is also used in these surgeries. Allograft cartilage is produced from donated human cartilage tissue. For easier use, this product is stored in 55% ethanol.
- the advantage of an allogeneic cartilage graft is that not only it fills the defect but also resists infection and is similar to an autogenous cartilage graft.
- the absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft.
- This product is biocompatible and its pH is equal to the physiological pH of the human body, which is suitable for planting stem cells and chondrocyte cells.
- Allograft cartilage is provided in sterile three-layer packages. This package should be checked completely before use so that it does not have any damage. Store this product in alcohol in the refrigerator at a temperature of (2-8 degrees Celsius) for up to two years.
- cartilage grafts plays an important role in plastic and reconstructive surgery, and it is used in various procedures such as nose surgery, ear repair, and other reconstructions. 26 Autograft cartilage transplantations were performed by Bert in 1865 for the first time. Then, in 1896, autologous cartilage transplantation was performed in humans by Koenig. Transplanted cartilage was used by Mangoldt in rhinoplasty surgery in 1900. The composite graft was reported in 1943 by Gillies for use in the tip of the nose.
- artificial materials such as TFE2 and polyethylene are used for secondary surgeries due to the limited access to cartilage, which is sometimes reported as the first line of treatment.
- silicone and cartilage or cartilage and microplate are used together.
- a good graft The characteristics of a good graft include its availability, absence of pain and complications at the site, easy tolerability, and lack of tendency to tear and puncture the skin or mucosa.
- a suitable graft should not change its shape and position and have the least absorption in the long term.
- xenograft was sometimes used in rhinoplasty, which was usually made of cow cartilage, which triggered the immune system and caused allergy and inflammation, and resulted in cartilage graft absorption.
- autograft due to features such as less inflammatory response as well as less absorption and less infection is selectively used compared to allograft and xenograft.
- the immune response seen in cartilage chondrocytes is type 2.
- cartilage grafts are one of the pillars of reconstruction in surgical operations, and in many cases, it is required to use these grafts in revision repeat surgeries. Also, as the years have passed, there have been advancements in the method of using these cartilages and new methods have replaced the old ones.
- Cartilage is composed of chondrocytes and an intercellular matrix, which are proteoglycan, elastic fibers, and collagen. Cartilage is divided into three types: hyaline, fibrocartilage, and elastic, of which the most common type is hyaline.
- Nasal septum cartilage and rib cartilage are of a hyaline type and human ear cartilage is of elastic cartilage type. Normally, rib cartilage or ear or nasal septum are used for cartilaginous nasal grafts. Due to this limitation, various other materials have been used in patients, including silicone and Medpor prostheses.
- Human cartilages are cartilages processed by the organ transplant bank, which are taken from another person and are protected from infectious diseases, for use by patients, and usually, the cartilages of young people less than 45 years old are used because they are not calcified. Donors are checked for malignancy, metastasis, use of intravenous opioid drugs, and diseases such as AIDS and hepatitis, and then their cartilage is stored in an ethanol solution.
- animal cartilage may also be available in some cases and used in surgery. Because cartilage is a relatively simple but specialized tissue that consists of extracellular material and chondrocyte cells and does not have an internal vascular network, therefore, it has weak antigenic properties and causes low levels of the immune response. Allograft cartilage has been widely used since the mid-20 th century. Because chondrocyte cells are surrounded by an extracellular matrix and are not directly related to blood vessels, the cells survive for a very long time.
- cartilage grafts plays an important role in plastic and reconstructive surgery, and the human body has limited resources for cartilage harvesting. Therefore, allograft cartilage is also used in these surgeries. Allograft cartilage is prepared using donated human cartilage tissue. For easier use, this product is stored in 55% ethanol.
- the advantage of an allogeneic cartilage graft is that not only it fills the defect but also is resistant to infection and is similar to an autogenous cartilage graft. The absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft.
- This product is biocompatible and its pH is equal to the physiological pH of the human body, which is suitable for planting stem cells and chondrocyte cells.
- This product is used for septorhinoplasty, jaw, face, E.N.T., and plastic surgery, and repair as well as reconstruction. Allograft cartilage is provided in sterile three-layer packages. This package should be checked completely before use so that it does not have any damage. Store this product in alcohol in the refrigerator at a temperature of (2-8 degrees celsius) for up to two years.
- Allograft cartilage is prepared from donated human cartilage tissue. For easier use, this product is stored in 55% ethanol.
- the advantage of allogeneic cartilage graft is that it not only fills the defect but also is resistant to infection and is similar to autogenous cartilage graft.
- the absorption rate of allogeneic cartilage graft is almost the same as that of autogenous cartilage graft.
- the product After production, the product can be stored for 2 years in hospital pharmacies in a normal refrigerator, and it is used to repair body tissues of patients in need, and its main uses are:
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Abstract
The human hyaline cartilage products with the origin of costal cartilage, articular cartilage, and nasal septum cartilage are irradiated and preserved in alcohol. Allograft cartilage is taken from donated human cartilage tissue. The advantage of an allogeneic cartilage graft is that not only does it fill the defect but also resists infection and is similar to an autogenous cartilage graft. The absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft. In this process (the mentioned invention), a concentration of 55% alcohol solution is used, which in addition to benefiting from the method of keeping the product in alcohol (which is much easier than keeping it in the freezing condition) it prevents the removal of the desired moisture content of the product by alcohol (preventing dehydration of the product and damage to its biomechanics).
Description
The human hyaline cartilage products with the origin of costal cartilage, articular cartilage, and nasal septum cartilage are irradiated and preserved in alcohol. Allograft cartilage is taken from donated human cartilage tissue. The advantage of an allogeneic cartilage graft is that not only does it fill the defect but also resists infection and is similar to an autogenous cartilage graft. The absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft. In this process (the mentioned invention), a concentration of 55% alcohol solution is used, which in addition to benefiting from the method of keeping the product in alcohol (which is much easier than keeping it in the freezing condition) it prevents the removal of the desired moisture content of the product by alcohol (preventing dehydration of the product and damage to its biomechanics)
A61K, A61P
In the historical cohort study, 179 patients who had, primarily and secondarily, visited the plastic surgery clinic for rhinoplasty surgery, underwent surgery, and needed cartilage grafts were selected. Patients with diabetes or autoimmune disease were excluded from the study. Also, the patients who did not show up regularly for periodical examinations were excluded from the study.
124 out of 179 selected patients were included in the study. Autograft cartilage was used in 79 patients and allograft cartilage was used in 45 patients. A standard photograph was taken of all patients upon entering the study. All patients underwent open rhinoplasty surgery, which is the preferred method from the surgeon's point of view and allows cartilage graft placement in the right place. In patients who needed cartilage grafts, autograft cartilage was used as much as possible. The initial place of harvesting was from the cartilaginous wall of the nose and then from the cartilage of the ear. In this study, allograft cartilage was used in patients who did not have enough cartilage to use, or there were no suitable conditions for preparing their cartilage, for example, patients who did not agree to remove cartilage from the rib or ear, or due to previous cystoplasty, the patient did not have enough septal cartilage.
In this study, patients were divided into two groups. The first group was patients who used cartilage grafts from their own body (autogenous) for nasal reconstruction, and the second group was patients who used allograft cartilage due to limited access to autograft cartilage. In the second group of patients, since it was not possible to use their nose septum or ear cartilage, with their informed consent, cartilage processed by the organ transplant bank was used for them. The cartilage that was used was, before the operation, divided and shaped into pieces of different sizes for use in different parts of the nose. All patients were given one gram of cefazolin as a prophylactic antibiotic, one hour before the operation, and continued for one day after the operation. Next, we will look at international methods, and it should be noted that none of these proposals are the same as the mentioned proposal.
Supports and methods for promoting the integration of cartilage tissue explants
United States Patent 10167447
The present disclosure provides tissue supports and methods for preparing a cartilage composition for repairing cartilage defects, which is prepared by expanding and integrating small cartilage tissue pieces derived from a donor or engineered tissue. The methods and supports described herein promote cell migration and integration of neighboring tissue pieces in culture to form the cartilage composition. Methods of cartilage repair using the cartilage composition are also described.
Method of obtaining viable small tissue particles and use for tissue repair
United States Patent 8497121
The invention provides a composition including isolated small living tissue particles, a method of making the tissue particles, and a method of using the composition to ameliorate a tissue defect. The tissue particles are composed of cells and their associated extracellular molecules and are sized, in certain embodiments, to be smaller than about 1 mm. Another aspect of the inventive tissue particles is the large percentage of viable cells. In certain embodiments, the tissue particles are made from cartilage and the composition may also contain additives such as adhesives, solutions, and bioactive agents.
METHOD FOR REPAIRING AND PROLIFERATING CARTILAGE TISSUE AND METHOD OF CARTILAGE DEFECT TREATMENT
United States Patent Application 20130344115
A method for repairing cartilage tissues includes the following steps: adhering a plurality of endothelial progenitor cells onto a scaffold to form a composition and implanting the composition into an individual. The present invention also provides a method of cartilage defect treatment and a method for proliferating cartilage tissues. The methods in accordance with the present invention are advantageous for safely and quickly repairing or proliferating cartilage tissues for disease treatment and physical function maintenance.
PROTECTING AND REPAIRING CARTILAGE AND MUSCULOSKELETAL SOFT TISSUES
United States Patent Application 20120021986
Provided herein are compositions and methods related to promoting the protection or repair of articular cartilage and/or musculoskeletal soft tissue by contacting the cartilage, tissues, or cellular components thereof with a parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor agonist or releasing factor.
The use of cartilage grafts plays an important role in plastic and reconstructive surgery, and the human body has limited resources for cartilage harvesting. Therefore, allograft cartilage is also used in these surgeries. Allograft cartilage is produced from donated human cartilage tissue. For easier use, this product is stored in 55% ethanol. The advantage of an allogeneic cartilage graft is that not only it fills the defect but also resists infection and is similar to an autogenous cartilage graft. The absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft. This product is biocompatible and its pH is equal to the physiological pH of the human body, which is suitable for planting stem cells and chondrocyte cells. This product is used for septorhinoplasty, jaw, face, E.N.T., and plastic surgery, and repair as well as reconstruction. Allograft cartilage is provided in sterile three-layer packages. This package should be checked completely before use so that it does not have any damage. Store this product in alcohol in the refrigerator at a temperature of (2-8 degrees Celsius) for up to two years.
The use of cartilage grafts plays an important role in plastic and reconstructive surgery, and it is used in various procedures such as nose surgery, ear repair, and other reconstructions. 26 Autograft cartilage transplantations were performed by Bert in 1865 for the first time. Then, in 1896, autologous cartilage transplantation was performed in humans by Koenig. Transplanted cartilage was used by Mangoldt in rhinoplasty surgery in 1900. The composite graft was reported in 1943 by Gillies for use in the tip of the nose. In the 1990s, the number of patients who used cartilage grafts in rhinoplasty was reported to be much higher than in the previous decade, and in contrast, surgical complications and the number of secondary rhinoplasty surgeries decreased significantly, and the amount of cartilage allografts used compared to autografts also decreased, which was due to the fear of transmission of infection from the donor to the recipient, after which it was proven in subsequent studies that due to the preparation of cartilage and the absence of blood and its products, the possibility of transmission of HIV is very low and so is the possibility of transmission of other infections. On the other hand, in the autograft cartilage of the ear or rib, a new scar site is formed in the patient, and there is a possibility of keloid, pain after the operation, pleural membrane damage, pneumothorax, hemothorax, and the surgery to remove the cartilage increases the operation time and the cost of the operation. Silicone prostheses are sometimes used in rhinoplasty patients.
Also, in some cases, artificial materials such as TFE2 and polyethylene are used for secondary surgeries due to the limited access to cartilage, which is sometimes reported as the first line of treatment. In some patients, silicone and cartilage or cartilage and microplate are used together.
The characteristics of a good graft include its availability, absence of pain and complications at the site, easy tolerability, and lack of tendency to tear and puncture the skin or mucosa. In addition, a suitable graft should not change its shape and position and have the least absorption in the long term. In the past, xenograft was sometimes used in rhinoplasty, which was usually made of cow cartilage, which triggered the immune system and caused allergy and inflammation, and resulted in cartilage graft absorption. Usually, autograft due to features such as less inflammatory response as well as less absorption and less infection is selectively used compared to allograft and xenograft. The immune response seen in cartilage chondrocytes is type 2.
These cartilage grafts are one of the pillars of reconstruction in surgical operations, and in many cases, it is required to use these grafts in revision repeat surgeries. Also, as the years have passed, there have been advancements in the method of using these cartilages and new methods have replaced the old ones. In the human body, there are limited sources for cartilage removal, which include the nasal septum, external ear, and ribs, each of which has its complications. Cartilage is composed of chondrocytes and an intercellular matrix, which are proteoglycan, elastic fibers, and collagen. Cartilage is divided into three types: hyaline, fibrocartilage, and elastic, of which the most common type is hyaline. Nasal septum cartilage and rib cartilage are of a hyaline type and human ear cartilage is of elastic cartilage type. Normally, rib cartilage or ear or nasal septum are used for cartilaginous nasal grafts. Due to this limitation, various other materials have been used in patients, including silicone and Medpor prostheses.
Human cartilages (Allograft or homologous) are cartilages processed by the organ transplant bank, which are taken from another person and are protected from infectious diseases, for use by patients, and usually, the cartilages of young people less than 45 years old are used because they are not calcified. Donors are checked for malignancy, metastasis, use of intravenous opioid drugs, and diseases such as AIDS and hepatitis, and then their cartilage is stored in an ethanol solution.
In addition, animal cartilage (Xenograft) may also be available in some cases and used in surgery. Because cartilage is a relatively simple but specialized tissue that consists of extracellular material and chondrocyte cells and does not have an internal vascular network, therefore, it has weak antigenic properties and causes low levels of the immune response. Allograft cartilage has been widely used since the mid-20th century. Because chondrocyte cells are surrounded by an extracellular matrix and are not directly related to blood vessels, the cells survive for a very long time. In numerous studies, both clinical and laboratory, the use of allograft cartilage has had different success rates, and the survival time of the patient's own cartilage(autograft) is the longest, whereas the animal cartilage(xenograft) has the shortest survival time and the survival time of other humans’ cartilage(allograft) is somewhere in between.
The use of human cartilage (graft) has been of interest to surgeons for many years. But our product has improved the following cases due to its special production process:
- Other products are stored and transported in a frozen form in the world, but in the product prepared by this process, there is no need for frozen storage conditions.
- In addition to radiation, during its process, this product is stored in alcohol as well, which reduces the risk of infection transmission to the recipient of the product (patient).
- In this product, cuts and slicing operations are performed in the production process, and products that are bent are removed before the final packaging of the product, therefore we will not see any problems after using the product.
- Keeping cartilage tissue in 70-degree alcohol, which is routinely used in medicine, removes the natural moisture of the cartilage tissue and causes fragility and damage to the biomechanics of the product. But in this process (the mentioned invention), we have achieved a concentration of alcohol solution that, in addition to benefiting from the method of keeping the product in alcohol (which is much easier than keeping it in frozen conditions), prevents the removal of the desired moisture of the product by alcohol (preventing product dehydration and damage to its biomechanics)
The use of cartilage grafts plays an important role in plastic and reconstructive surgery, and the human body has limited resources for cartilage harvesting. Therefore, allograft cartilage is also used in these surgeries. Allograft cartilage is prepared using donated human cartilage tissue. For easier use, this product is stored in 55% ethanol. The advantage of an allogeneic cartilage graft is that not only it fills the defect but also is resistant to infection and is similar to an autogenous cartilage graft. The absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft.
This product is biocompatible and its pH is equal to the physiological pH of the human body, which is suitable for planting stem cells and chondrocyte cells. This product is used for septorhinoplasty, jaw, face, E.N.T., and plastic surgery, and repair as well as reconstruction. Allograft cartilage is provided in sterile three-layer packages. This package should be checked completely before use so that it does not have any damage. Store this product in alcohol in the refrigerator at a temperature of (2-8 degrees celsius) for up to two years.
The production steps of this product are as follows:
- Receiving rib cartilage, nasal septum, or joint surface, isolated in the operating room
- Soft tissue dissection (muscles, perichondrium, and cancellous bone under the joint surface)
- Washing and taking tissue samples for quality control tests
- Slicing and spreading the cartilage to the desired dimensions and thickness and observing the tissue cutting conditions to reduce subsequent warping.
- Keep at 70-degree alcohol for 15 minutes
- Storage in alcohol at 55 degrees for 2 weeks in the refrigerator
- Checking the results of quality control tests and removing bent and twisted parts from the product as well as non-conforming products.
- Packing 3 layers of tissue in a medical grade polyethylene container in 55-degree alcohol + accompanying documents
- Irradiation of the product with 25 kGy of gamma rays
- Performing sterility tests on the final product
- Releasing the product in medical centers
Process and sterilization method
After screening the donors and confirming their health, by evaluating their medical history and physical examination, with an age limit between 15 and 45 years, quality control tests are performed using microbiological and serological tests. Each sample is tested for aerobic and anaerobic bacteria, fungi, antibodies against HIV type 1 and 2, (anti-HIV1&2), T-lymphotropic virus type 1 and 2 antibodies (anti-HTLV-1/2), hepatitis B antibody (HBcAb), hepatitis B surface antigen, hepatitis C virus antibody (HCVAb) and RPR for syphilis. HIV, HCV, and HBV PCR tests are also required. Before sterilization and manufacturing process, final validation is done for the tissue.
Preventing subsequent warping of the product in the patient's body
Much simpler storage and transfer and no need for freezing conditions
Better preservation of physical and biomechanical properties of the product
The unique price of the cartilage product of the septum and the cartilage plates of the human hyaline joint among all the leading manufacturers in the world
Avoid dehydration of the product compared to the conditions of routine storage of products in alcohol
The use of articular hyaline cartilage plate from cadaver consumers, which will make a large amount of the product available and has a suitable function as a nasal septum (and without access restrictions).
Examples
Allograft cartilage is prepared from donated human cartilage tissue. For easier use, this product is stored in 55% ethanol. The advantage of allogeneic cartilage graft is that it not only fills the defect but also is resistant to infection and is similar to autogenous cartilage graft. The absorption rate of allogeneic cartilage graft is almost the same as that of autogenous cartilage graft.
After production, the product can be stored for 2 years in hospital pharmacies in a normal refrigerator, and it is used to repair body tissues of patients in need, and its main uses are:
- Severe injuries to the face and nose in an accident
- Rhinoplasty surgery that requires cartilage tissue.
- Reconstructing the external ear in children and infants who have not had congenitally formed ears.
- Wide holes in the blade separating the two sides of the nose
Claims (7)
- The human hyaline cartilage products with the origin of costal cartilage, articular cartilage, and nasal septum cartilage are irradiated and preserved in alcohol. Allograft cartilage is taken from donated human cartilage tissue. The advantage of an allogeneic cartilage graft is that not only does it fill the defect but also resists infection and is similar to an autogenous cartilage graft. The absorption rate of an allogeneic cartilage graft is almost the same as that of an autogenous cartilage graft.
- This product is an improvement compared to other products due to the processing done and it is no longer necessary to freeze the product for its storage.
- In addition to radiation, this product is also stored in alcohol in its process, which reduces the risk of infection transmission to the recipient of the product (patient).
- In this product, cuts and slicing operations are performed in the production process, and products that are bent are removed before the final packaging of the product, therefore we will not see any problems after using the product.
- In this process (the mentioned invention), a concentration of 55% alcohol solution is used, which in addition to benefiting from the method of keeping the product in alcohol (which is much easier than keeping it in the freezing condition) it prevents the removal of the desired moisture content of the product by alcohol (preventing dehydration of the product and damage to its biomechanics)
- This product is biocompatible and its pH is equal to the physiological pH of the human body, which is suitable for planting stem cells and chondrocyte cells.
- The production steps of this product are as follows:
- Receiving costal cartilage, nasal septum cartilage, or an articular surface, isolated in the operating room
- Soft tissue dissection (muscles, perichondrium, and cancellous bone under the joint surface)
- Washing and taking tissue samples for quality control tests
- Slicing and spreading the cartilage to the desired dimensions and thickness and observing the tissue cutting conditions to reduce subsequent warping.
- Keep at 70-degree alcohol for 15 minutes
- Store in alcohol at 55 degrees for 2 weeks in the refrigerator
- Check the results of quality control tests and remove bent and twisted parts from the product as well as non-conforming products.
- Packing 3 layers of tissue in a medical grade polyethylene container in 55-degree alcohol + accompanying documents
- Irradiation of the product with 25 kGy gamma rays
- Performing sterility tests on the final product
- Release the product in medical centers
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Citations (4)
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EP0511430B1 (en) * | 1991-05-01 | 1997-10-08 | Cytyc Corporation | Cell preservative solution |
US20080077251A1 (en) * | 1999-06-07 | 2008-03-27 | Chen Silvia S | Cleaning and devitalization of cartilage |
CN111657267B (en) * | 2020-06-17 | 2021-02-02 | 科瑞百奥泰州生物技术有限公司 | Ice-free crystal frozen preservation solution and freezing method for preservation of cartilage, tendon and meniscus |
CN110507855B (en) * | 2019-09-05 | 2022-04-19 | 南京屹特博医学科技发展有限公司 | Preparation method of heterogenous costal cartilage for local support effect |
-
2023
- 2023-02-03 WO PCT/IB2023/050992 patent/WO2024013571A1/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0511430B1 (en) * | 1991-05-01 | 1997-10-08 | Cytyc Corporation | Cell preservative solution |
US20080077251A1 (en) * | 1999-06-07 | 2008-03-27 | Chen Silvia S | Cleaning and devitalization of cartilage |
CN110507855B (en) * | 2019-09-05 | 2022-04-19 | 南京屹特博医学科技发展有限公司 | Preparation method of heterogenous costal cartilage for local support effect |
CN111657267B (en) * | 2020-06-17 | 2021-02-02 | 科瑞百奥泰州生物技术有限公司 | Ice-free crystal frozen preservation solution and freezing method for preservation of cartilage, tendon and meniscus |
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