TR201908115A2 - BIOACTIVE TISSUE SCAFFOLDING WITH MUCUS AND SLIME BASED GRADIAN LAYER - Google Patents
BIOACTIVE TISSUE SCAFFOLDING WITH MUCUS AND SLIME BASED GRADIAN LAYER Download PDFInfo
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Classifications
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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
- A61L27/38—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 containing added animal cells
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- 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
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
-
- 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
Abstract
Buluş, sağlık sektöründe, özellikle rejeneratif tıp alanında, kemik, kıkırdak ve eklem hasarlarına yönelik olup, hasarların onarımı için biyolojik malzemeler içeren gradyan katmanlı doku iskelesi (1) olup, özelliği; vücuda implante edildiğinde kemik dokuya temas eden bir alt katman (3) ve kıkırdak dokuya temas eden bir üst katman (2) içermesi, bahsedilen üst katman (2) ve alt katmanın (3) gradyan geçişli olması, üst katmanda (2) yer alan kitosan matriks içindeki mukus veya slime oranının, alt katmanda (3) yer alan kitosan matriks içindeki mukus veya slime oranından daha düşük olması ile karakterize edilmesidirThe invention is directed to bone, cartilage and joint damages in the health sector, especially in the field of regenerative medicine, and it is a gradient layered tissue scaffold (1) containing biological materials for repairing the damages, When implanted in the body, it contains a lower layer (3) that contacts the bone tissue and an upper layer (2) that touches the cartilage tissue, the upper layer (2) and the lower layer (3) have gradient transition, the chitosan in the upper layer (2) characterized in that the ratio of mucus or slime in the matrix is lower than the ratio of mucus or slime in the chitosan matrix in the substrate (3).
Description
TARIFNAME MUKUS VE SLIME TEMELLI GRADYAN KATMANLI BIYOAKTIF DOKU Teknolojik Alan: Bulus, saglik sektöründe, özellikle rejeneratif tip alaninda, kemik, kikirdak ve eklem hasarlarina yönelik olup, hasarlarin onarimi için kitosan, mukus ve slime biyolojik malzemelerini içeren gradyan katmanli doku iskelesi ile ilgilidir. DESCRIPTION GRADIANT LAYER BIOACTIVE TISSUE BASED ON MUCUS AND SLIME Technological Field: The invention is used in the health sector, especially in the field of regenerative medicine, in bone, cartilage and for joint damage, chitosan, mucus and slime for repair of damage It relates to a gradient layered scaffold containing biological materials.
Bulus özellikle, kikirdak veya osteokondral defektlerin tamirini ve tedavisini saglamak üzere gradyan katmanli bir doku iskelesi ile ilgilidir. In particular, the invention focuses on the repair and treatment of cartilage or osteochondral defects. It relates to a gradient layered scaffold to provide
Teknigin Bilinen Durumu: Bilinen teknikte, uzun yillardir kas ve iskelet sistemindeki kikirdak veya kemik hasarlarinda protezler kullanilmaktadir. Bahsedilen protez cerrahisi, geri dönüsü olmayan, düsük biyouyumlu ve pahali bir tedavidir. Protez harici tedavi yöntemlerinde greft materyalleri kullanilmaktadir. Yapilan arastirmalarda, doku iskelelerinin greft materyallerine göre birçok avantajinin bulundugu, bu doku iskelelerinin greft materyallere alternatif olacak, biyoaktif bir tedavi yöntemi olarak kullanilabilecegini göstermistir. Doku mühendisligi, degisen dokularin islevlerini önemli ölçüde yenileyebilen, biyolojik ikame maddeleri gelistirmek için mühendislik ve biyolojik bilim ilkelerini birlestiren yeni bir disiplindir. Bu disiplin, biyo-malzemelerin, hücrelerin ve biyolojik veya çevresel faktörlerin "doku mühendisligi üçlüsü" olarak da bilinen bir birlesmesine dayanmaktadir. Son zamanlarda doku mühendisligi alaninda biyolojik kaynaklardan elde edilen malzemeler ile üretilen doku iskeleleri, uygun hücre kaynaklari ve / veya biyo- aktif sinyal moleküllerinin kullanimi hastalarda agri olusturan tedavilerin yerini almaktadir. Doku mühendisligi bilesenleri arasinda yer alan doku iskeleleri, hücrelerin tutunumu ve çogalmasi için üç boyutlu (BB) ortam saglama konusunda oldukça önemli bir role sahiptir. Doku iskeleleri dokuya uygun, gerektiginde stabil veya uygun bozunma hizinda olmali, vücuda uyumlu bilesenlerden olusmali ve gerekli mekanik dayanimi saglamalidir. Ayrica hücrelerin yerlesmesine izin veren, oksijen ve besin difüzyonuna imkan saglayan gözenekli yapiya sahip olmalidir. Doku iskelesi tasarlarken hedef, hücrelerin yasayip, çogalabildigi ve spesifik dokuya farklilasabildigi ve dogal ekstrasellüler matriks yapisinin yerini alabilecek ideal yapiyi elde etmektir. State of the Art: In the known technique, cartilage or bone in the musculoskeletal system has been used for many years. Prostheses are used for damage. The aforementioned prosthetic surgery, its return It is a non-invasive, low biocompatible and expensive treatment. prosthetic external treatment graft materials are used in the methods. In the researches, tissue scaffolds have many advantages over graft materials, this tissue a bioactive treatment method that will be an alternative to graft materials of scaffolds demonstrated that it can be used as Tissue engineering, changing tissues to develop biological substitutes that can significantly regenerate their functions. It is a new discipline that combines the principles of engineering and biological science. This discipline of biomaterials, cells, and biological or environmental factors It is based on a combination also known as the "engineering trio". obtained from biological sources in the field of tissue engineering scaffolds produced with materials, suitable cell sources and/or bio- The use of active signaling molecules has replaced pain-inducing treatments in patients. takes. Tissue scaffolds, which are among the tissue engineering components, providing a three-dimensional (BB) environment for cells to adhere and multiply plays a very important role in Tissue scaffolds are suitable for tissue, when necessary, it should be stable or at an appropriate rate of degradation, compatible with the body It should consist of components and provide the necessary mechanical strength. Moreover allowing oxygen and nutrient diffusion, allowing cells to settle It should have a porous structure that provides While designing the scaffold, the target is natural cells where cells can live, multiply and differentiate into specific tissue It is to obtain the ideal structure that can replace the extracellular matrix structure.
Tarifname konusu bulus hem protez hem de greft materyalleri yerine kullanilmak üzere gradyan katmanli bir doku iskelesi ortaya koymaktir. The invention, which is the subject of the description, replaces both prosthesis and graft materials. to reveal a gradient layered scaffold for use.
Kemik-kikirdak dokunun bir araya gelmesi ile olusan osteokondral dokunun, yaralanma veya dejeneratif hastaliklardan sonra kendini yenilemesi oldukça zordur. Osteokondral hasarlar için, artroplasti, subkondral drilleme, mikro kirik olusturma, mozaikplasti ve protez eklem replasmani gibi klinik tedaviler mevcuttur. Ancak bu yöntemlerin birçok dezavantaji bulunmaktadir. Bu dezavantajlara fizyolojik olarak doku hasari, cilt hasari ve cerrahi girisim sirasinda hastada olusan komplikasyonlar; biyolojik olarak ise enfeksiyon, doku uyumsuzlugu, vücut Içerisinde olusan immünolojik reaksiyonlar örnek verilebilir. Osteochondral tissue, which is formed by the combination of bone-cartilage tissue, self-renewal after injury or degenerative disease it is difficult. For osteochondral injuries, arthroplasty, subchondral drilling, micro fracture clinical treatments such as creation, mosaicplasty and prosthetic joint replacement available. However, these methods have many disadvantages. This Physiological tissue damage, skin damage and surgical intervention complications that occur in the patient during; biologically, infection, tissue incompatibility, immunological reactions occurring in the body can be given as examples.
Bu cerrahi girisimlerin yani sira, bilinen teknikte kemik, kikirdak ve eklem hasarlari için allogreft-otogreft uygulamalari mevcuttur. Ancak kullanilan yöntemlerin süregelen dezavantajlari bulunmaktadir. Genellikle, hasarlari tamamen ortadan kaldirmayan bu yöntemlerde; vücut içerisine implante edilen greft materyallerinin doku içerisinde enfeksiyon, cilt hasari, doku hasari ve doku uyumsuzlugu gibi birçok olumsuz biyolojik ve fizyolojik etkilesime neden olmaktadir. In addition to these surgical interventions, bone, cartilage and joint There are allograft-autograft applications for damage. However, used methods have persistent disadvantages. Usually, the damage In these methods, which do not completely eliminate; implanted in the body infection, skin damage, tissue damage and tissue cause many negative biological and physiological interactions such as incompatibility is happening.
Devletler patent dokümaninda, farkli gözenek büyüklüklerine sahip çok katmanli bir doku iskelesi olusturulmustur. Elde edilen doku iskelesi eklem kikirdagi onarimi için üretilmistir. Doku iskelesine sadece kikirdak hücreleri ekilmis ve çogaltilmistir. Tarifname konusu bulusta, hem kullanilan malzemeler farklidir hem de kemik ve kikirdak hücreleri gradyan katmanli doku iskelesinde ayni anda çogalabilmektedir. numarali Birlesik Devletler patent dokümaninda, osteokondral defekt onarimi için uygun çok katmanli bir kollajen doku iskelesini üretmek için bir yöntem ile ilgilidir. Ayrica patent çok katmanli bir kollajen kompozit doku iskelesi ve bunlarin osteokondral defekt onariminda kullanimlari ile de ilgilidir. Dokümanda, malzeme olarak kolajen, hidroksiapatit ve glikozaminoglikan (GAG) kullanilmistir. Her tabakada opsiyonel olarak farkli tipte kolajen kullanilmis ve hidroksiapatit ya da GAG eklenmistir. Üretim tekniginde tabakalarin olusturulma asamasi farklidir. In the state patent document, multilayers with different pore sizes A tissue scaffold was created. The resulting tissue scaffold is articular cartilage Made for repair. Only cartilage cells were seeded on the scaffold and has been multiplied. In the invention, which is the subject of the description, both the materials used are different. Both bone and cartilage cells are identical in gradient layer scaffolds. can be multiplied at the same time. Repair of osteochondral defect, in United States patent document No. by a method for producing a multilayer collagen scaffold suitable for is relevant. In addition, a patent multilayer collagen composite scaffold and It is also related to their use in osteochondral defect repair. In the document, collagen, hydroxyapatite and glycosaminoglycan (GAG) as materials used. Different types of collagen were optionally used in each layer and hydroxyapatite or GAG is added. Formation of layers in production technique stage is different.
Devletler patent dokümaninda, hem hiyalin hem elastik kikirdak yerine geçebilecek bir yapi üretilmistir. Ayrica gelistirilen doku iskelesi hücre tutunumu ve büyümesine imkan saglayacak sekilde olusturulmustur. Ancak yapi sadece kikirdak doku olusumuna yönelik olarak tasarlanmistir. Söz konusu patentte tuz çözeltisi varliginda gözenek olusturma, sinterleme gibi farkli metodlar kullanilarak suda çözünmeyen sentetik polimerlerden doku iskelesi üretimi tanimlanmistir. States replace both hyaline and elastic cartilage in their patent document. A structure that can pass has been produced. In addition, the developed scaffold cell adhesion and has been created in a way that allows it to grow. But just do It is designed for cartilage tissue formation. Salt in the patent in question Different methods such as pore formation, sintering in the presence of solution Fabrication of scaffolds from water-insoluble synthetic polymers using has been defined.
Yapilan bir diger literatür arastirmasinda karsilasilan GB2549714A numarali Birlesik Krallik patent dokümaninda, patentte kemik doku onarimi ve rejenerasyonu için otolog kemik iligi aspirati ve PRP'de bulunan anjiyojen c ve osteojenik hücrelerin tutunumuna izin veren, kalsiyum fosfat tozunu enkapsüle ederek elde edilen iki farkli biyolojik doku iskelesi tasarlanmistir. Ayrica doku iskelelerine büyüme faktörleri eklenmistir. Gelistirilen doku iskelesi sadece kemik doku onarimi için tasarlanmistir. GB2549714A, which was encountered in another literature search, In the United Kingdom patent document, bone tissue repair and Autologous bone marrow aspirate and angiogen c found in PRP for regeneration encapsulates calcium phosphate powder, allowing the attachment of osteogenic cells Two different biological tissue scaffolds obtained by Also texture Growth factors were added to the scaffolds. The developed scaffold is only Designed for bone tissue repair.
Yapilan bir diger literatür arastirmasinda karsilasilan CN102973981 numarali Çin patent dokümaninda, polihidroksibütirat valerik asit kopolesteri (PHBV), polioksietilen (PEO) ve nanohidroksiapatit (n-HA) kullanilarak, elektroegirme yöntemi ile üç katmanli doku iskelesi elde edilmistir. Doku iskelesi kemik doku onarimi için tasarlanmistir. CN102973981, which was encountered in another literature search. In the Chinese patent document, polyhydroxybutyrate valeric acid copolyester (PHBV), electrospinning using polyoxyethylene (PEO) and nanohydroxyapatite (n-HA) A three-layer tissue scaffold was obtained by the method. scaffold bone tissue It is designed for repair.
Yapilan bir diger literatür arastirmasinda karsilasilan CN104874027 numarali Çin patent dokümaninda, kontrollü ilaç salinimi yapabilen kemik doku iskelesi gelistirilmistir. Bu patentte kikirdak doku onarimi için bir yapidan bahsedilmemistir. CN104874027, which was encountered in another literature search. Bone tissue scaffold capable of controlled drug release in Chinese patent document developed. In this patent, a structure for cartilage tissue repair not mentioned.
Yapilan bir diger literatür arastirmasinda karsilasilan CN105435311 numarali Çin patent dokümaninda, çok katmanli bir doku iskelesi gelistirilmistir. Doku iskelesi; kikirdak doku katmani, kikirdak doku kalsifikasyon katmani, gözenekli bir hücre bölme membrani ve bir kemik doku katmanindan olusan çok katmanli bir entegre yapidir. Doku iskelesi mikro-nano hidroksiapatit kristaller, parçalanabilir non-stokiyometrik polietilen glikol / poli-s-kaprolakton nano- koaksiyel kisa elyaflar ve asilanmis RGD heparin sülfat / oksitlenmis sodyum aljinat içermektedir. Üretilen doku iskelesi eklem kikirdagi ve subkondral hasarlarin onarimi için gelistirilmistir. CN105435311, which was encountered in another literature search. In the Chinese patent document, a multilayer scaffold has been developed. Tissue jetty; cartilage tissue layer, cartilage tissue calcification layer, porous multilayered consisting of a cell dividing membrane and a layer of bone tissue It is an integrated structure. Scaffold micro-nano hydroxyapatite crystals, degradable non-stoichiometric polyethylene glycol / poly-s-caprolactone nano- coaxial short fibers and grafted RGD heparin sulfate / oxidized sodium Contains alginate. The tissue scaffold produced is articular cartilage and subchondral It is developed for repairing damages.
Yapilan bir diger literatür arastirmasinda karsilasilan CN204951735 numarali Çin patent dokümaninda, kemik-kikirdak doku için çok katmanli bir doku iskelesi elde edilmistir. Kemik doku katmani PLGA ve hidroksiapatit; kalsifiye katman tip olusmaktadir. Patentte gelistirilen doku iskelesi 3 boyutlu yazici kullanilarak üretilmistir. CN204951735, which was encountered in another literature search. A multilayer scaffold for bone-cartilaginous tissue in Chinese patent document has been obtained. Bone tissue layer PLGA and hydroxyapatite; calcified layer type is formed. Using a 3D printer, the tissue scaffold developed in the patent has been produced.
Yapilan bir diger literatür arastirmasinda karsilasilan CN102872480 numarali Çin patent dokümaninda, osteokondral doku için bifazik çok katmanli doku iskelesi üretilmistir. Doku iskelesinin gelistirilmesinde her bir tabaka için farkli polimer temelli kompozitler kullanilmistir ve bu malzemeler bizim bulusumuzda kullanilan malzemelerden farklidir. CN102872480, which was encountered in another literature search. In the Chinese patent document, biphasic multilayer tissue for osteochondral tissue scaffold is produced. In the development of the tissue scaffold, different polymer-based composites are used and these materials are used in our invention. different from the materials used.
Yapilan bir diger literatür arastirmasinda karsilasilan CN102861361 numarali Çin patent dokümaninda, biyomedikal alan için gradyan bir doku iskelesi elde edilmistir. Doku iskelesi manyetik kompozit nanopartiküllerden olusan bir hidrojeldir. Hidrojel; polivinil alkol veya hem polivinil alkol hem de dogal malzemeden olusmaktadir. Bu nedenle, bizim çalismamizdaki malzeme içerigi ve tasarimi açisindan farklilik göstermektedir. CN102861361, which was encountered in another literature search. In the Chinese patent document, a gradient scaffold for the biomedical field was obtained. has been made. The scaffold is composed of magnetic composite nanoparticles. is hydrogel. hydrogel; polyvinyl alcohol or both polyvinyl alcohol and natural consists of material. Therefore, the material content in our study and differ in design.
Sonuç olarak, mevcut sistemlerin birçok sorunlarini ortadan kaldiran, kemik kikirdak ve eklem hasarlarinin tedavisine yönelik yeni bir doku iskelesine ihtiyaç duyulmaktadir. As a result, the bone marrow, which eliminates many of the problems of existing systems, There is a need for a new tissue scaffold for the treatment of cartilage and joint damage. is heard.
Bulusun Kisa Açiklanmasi: Bulus, teknigin bilinen durumunun asildigi, dezavantajlarinin giderildigi, ilave olarak ekstra avantajlar içeren yeni bir doku iskelesidir. Brief Description of the Invention: The invention shows that the known state of the art is overcome, its disadvantages are eliminated, additional It is a new tissue scaffold with extra advantages.
Bulusun amaci; kemik, kikirdak ve eklem hasarlarinin tedavisine yönelik hedef doku morfolojisini taklit edebilen alternatif bir gradyan katmanli doku iskelesi ortaya koymaktir. The purpose of the invention; target for the treatment of bone, cartilage and joint damage an alternative gradient layer scaffold that can mimic tissue morphology is to reveal.
Bulusun bir diger amaci, hem kikirdak hem de kemik hasarinin oldugu bölgeyi tedavi edici biyolojik özellige sahip, gradyan yapida ve geçisli katmanlar içeren yeni bir doku iskelesi ortaya koymaktir. Another object of the invention is to examine the area where both cartilage and bone damage are present. It has therapeutic biological properties, has a gradient structure and contains transitional layers. to reveal a new tissue scaffold.
Bulusun bir diger amaci, farkli hücre yerlesme ve tutunmasina imkan saglayan üç boyutlu yapi ve morfolojiye sahip, biyoaktif ve biyouyumlu yapida yeni bir gradyan katmanli doku iskelesi ortaya koymaktir. Another aim of the invention is to allow different cell placement and attachment. a new bioactive and biocompatible structure with three-dimensional structure and morphology. to reveal a gradient layered scaffold.
Bulusun bir diger amaci, olusumunda kullanilan bütün bilesenler antimikrobiyal özelliklere sahip, vücut içerisine implante edildiginde biyouyumluluk gösteren ve enfeksiyon olusumunu engelleyen gradyan katmanli yeni bir doku iskelesi ortaya koymaktir. Another object of the invention is that all the components used in its formation are antimicrobial. properties, biocompatibility when implanted in the body, and a new scaffold with gradient layer that inhibits infection formation is to reveal.
Yukarida bahsedilen ve asagidaki detayli anlatimdan ortaya çikacak tüm amaçlari gerçeklestirmek üzere mevcut bulus, saglik sektöründe, özellikle rejeneratif tip alaninda, kemik, kikirdak ve eklem hasarlarina yönelik olup, hasarlarin onarimi için biyolojik malzemeler içeren doku iskelesi olup, özelligi; vücuda implante edildiginde kemik dokuya temas eden bir alt katman ve kikirdak dokuya temas eden bir üst katman içermesi, bahsedilen üst katman ve alt katmanin gradyan geçisli olmasi, bu gradyan geçisin farkli oranda mukus veya slime kullanilarak elde edilmesidir. Bu tasarimda tabakali yapi, üst katmanda yer alan kitosan matriks içindeki mukus veya slime oraninin alt katmanda yer alan kitosan matriks içindeki mukus veya slime oranindan daha düsük olmasi ile karakterize edilmistir. All the above-mentioned and the following will emerge from the detailed explanation. In order to achieve the objectives of the present invention, in the health sector, especially In the field of regenerative medicine, it is intended for bone, cartilage and joint damage, It is a tissue scaffold containing biological materials for the repair of damages, and its feature is; a substrate that contacts bone tissue when implanted in the body, and containing an upper layer in contact with the cartilage tissue, said upper layer and the lower layer has a gradient transition, this gradient transition has a different amount of mucus or using slime. In this design, the layered structure the lower part of the mucus or slime ratio in the chitosan matrix in the layer than the mucus or slime ratio in the chitosan matrix in the layer. characterized by its low
Bulusun tercih edilen bir diger yapilanmasinin özelligi; kitosan matriks içinde mukus içermesi ile kitosan-mukus olabilmesidir. Another preferred embodiment of the invention is characterized by; in chitosan matrix It can be chitosan-mucus by containing mucus.
Bulusun tercih edilen bir diger yapilanmasinin özelligi; kitosan matriks içinde slime içermesi ile (4) kitosan-slime olabilmesidir. Another preferred embodiment of the invention is characterized by; in chitosan matrix It can be chitosan-slime with its slime content (4).
Bulusun tercih edilen bir diger yapilanmasinin özelligi; üst katmanin kikirdak dokuyu taklit edebilmeye yönelik, üst katman mukus veya slime oraninin, alt katmana oranla düsük olmasidir. Another preferred embodiment of the invention is characterized by; cartilage of the upper layer to imitate the tissue, the upper layer mucus or slime ratio, the lower is low compared to the layer.
Bulusun tercih edilen bir diger yapilanmasinin özelligi; alt katmanin kemik dokuyu taklit edebilmeye yönelik, alt katman mukus veya slime oraninin, üst katmana oranla yüksek olmasidir. Another preferred embodiment of the invention is characterized by; bone of the substrate to mimic the tissue, the lower layer mucus or slime ratio, the upper higher than that of the layer.
Bulusun tercih edilen bir diger yapilanmasinin özelligi; her katmanda farkli yogunlukta ekstrakt olmak üzere, üst katmanda yer alan gözenek yapisinin, alt katmanda yer alan gözenek yapisindan farkli olmasidir. Another preferred embodiment of the invention is characterized by; different in each layer Density of the extract, the pore structure in the upper layer, the lower It is different from the pore structure in the layer.
Bulusun tercih edilen bir diger yapilanmasinin özelligi; kemik ve kikirdak biyobelirteçlerinin olusmasina imkan verecek gradyan geçisli üst katman ve alt katman içermesidir. Another preferred embodiment of the invention is characterized by; bone and cartilage gradient transition top layer and bottom layer that will allow the formation of biomarkers contains layers.
Bulusun tercih edilen bir diger yapilanmasinin özelligi; alt katman ve üst katmanin dondurarak kurutma (freze-drying) yöntemi ile üretilmesidir. Another preferred embodiment of the invention is characterized by; bottom layer and top is the production of the layer by freeze-drying (milling-drying) method.
Sekillerin Açiklanmasi: Bulus, ilisikteki sekillere atifta bulunularak anlatilacaktir, böylece bulusun özellikleri daha net anlasilacaktir. Ancak, bunun amaci bulusu bu belli düzenlemeler ile sinirlamak degildir. Tam aksine, bulusun ilisikteki istemler tarafindan tanimlandigi alani içine dâhil edilebilecek bütün alternatif, degisiklik ve denkliklerinin kapsanmasi da amaçlanmistir. Gösterilen ayrintilar, sadece mevcut bulusun tercih edilen düzenlemelerinin anlatimi amaciyla gösterildigi ve hem yöntemlerin sekillendirilmesinin, hem de bulusun kurallari ve kavramsal özelliklerinin en kullanisli ve kolay anlasilir tanimini saglamak amaciyla sunulduklari anlasilmalidir. Bu çizimlerde; Sekil-1 Bulus konusu gradyan katmanli doku iskelesi temsili görünümüdür. Explanation of Figures: The invention will be described with reference to the accompanying figures, so that the invention features will become clearer. However, the purpose of this is clear It's not about limiting yourself with regulations. On the contrary, the appended claims of the invention All alternatives, amendments, which may be included in the area in which it is defined by and equivalences are also intended to be covered. Details shown are only illustrated for illustration of preferred embodiments of the present invention, and both the shaping of the methods and the rules of the invention and the conceptual in order to provide the most useful and easy-to-understand description of its properties. presented must be understood. In these drawings; Figure-1 Representation of the gradient layered scaffold, the subject of the invention is the view.
Bu bulusun anlasilmasina yardimci olacak sekiller ekli resimde belirtildigi gibi numaralandirilmis olup isimleri ile beraber asagida verilmistir. Figures to assist in understanding this invention are as indicated in the attached picture. are numbered and given below with their names.
Referanslarin Açiklanmasi: 1. Gradyan katmanli doku iskelesi 2. Üst katman 3. Alt katman 4. Kitosan matriks içindeki mukus veya slime orani . Gözenek Bulusun Açiklanmasi: Bu detayli açiklamada bulus konusu gradyan katmanli doku iskelesi (1) sadece konunun daha iyi anlasilmasina yönelik olarak, hiçbir sinirlayici etki olusturmayacak örneklerle açiklanmaktadir. Tarifnamede, saglik sektöründe, özellikle rejeneratif tip alaninda, kemik, kikirdak ve eklem hasarlarina yönelik olup, hasarlarin onarimi için kitosan, mukus ve slime biyolojik malzemelerini içeren gradyan katmanli doku iskelesi (1) anlatilmaktadir. Explanation of References: 1. Gradient layer scaffold 2. Top layer 3. Substrate 4. The ratio of mucus or slime in the chitosan matrix . Pore Description of the Invention: In this detailed description, the inventive gradient layer scaffold (1) is only no limiting effect for a better understanding of the subject explained with examples. In the specification, in the health sector, for bone, cartilage and joint damage, especially in the field of regenerative medicine and it uses chitosan, mucus and slime biological materials to repair the damages. The gradient layered tissue scaffold (1) containing it is described.
Sekil 1' de bulus konusu gradyan katmanli doku iskelesi (1) temsili görünüm verilmektedir. Buna göre gradyan katmanli doku iskelesi (1) bir üst katman (2) ve bir alt katmandan (3) meydana gelmektedir. Üst katman (2) ve alt katmanda (3) kitosan matriks içinde mukus veya slime orani (4) bulunmaktadir. In Figure 1, the gradient layered scaffold of the invention (1) is representative view. are given. Accordingly, the gradient layer scaffold (1) is a top layer (2). and a substrate (3). On top layer (2) and bottom layer (3) There is a mucus or slime ratio (4) in the chitosan matrix.
Bahsedilen kitosan matriks içindeki mukus veya slime orani (4) kitosan-mukus veya kitosan-slime içerikli olabilmektedir. Böylelikle ayni islevi gören iki farkli içerik ve mikroyapiya sahip gradyan katmanli doku iskelesi (1) olusmaktadir. The ratio of mucus or slime in the aforementioned chitosan matrix (4) chitosan-mucus or chitosan-slime content. Thus, two different Gradient layered scaffold (1) with content and microstructure is formed.
Gradyan katmanli doku iskelesinin (1) üst katmani (2) kikirdak dokusunu taklit etmek üzere kitosan matriks içinde daha düsük mukus veya slime orani (4) içermektedir. Alt katmani (3) ise, kemik dokusunu taklit etmek üzere kitosan matriks içinde daha fazla mukus veya slime orani (4) içermektedir. Üst katman (2) ve alt katman (3) geçisli gözenek yapilari (5) içermektedir. Sekilden de anlasilacagi üzere, üst katmanda (2) yer alan gözeneklerin (5) yapisi alt katmandaki (3) gözeneklerin (5) yapisindan farkli olup gradyan katmanli doku iskelesi (1) her katmanda farkli yogunlukta ekstrakt olacak sekilde yapilandirilmistir. Bu sayede, üst katman (2) kikirdak dokusunu taklit eden yapiya sahip iken, alt katman (3) kemik dokusunu taklit eden mikroyapiya sahiptir. Bulus konusu gradyan katmanli doku iskelesi (1), vücuda implante edildiginde, temas yüzeyleri arasinda hücresel aktivasyonlar ile olusan yeni hücreler hem kikirdak hem de kemik hasarinin oldugu bölgeyi tedavi edici yapida olmaktadir. The top layer (2) of the gradient layer scaffold (1) mimics cartilage tissue lower mucus or slime rate in the chitosan matrix (4) contains. The bottom layer (3) is chitosan to imitate bone tissue. contains more mucus or slime ratio (4) in the matrix. top layer (2) and the substrate (3) contain transitional pore structures (5). from the figure As it can be understood, the structure of the pores (5) in the upper layer (2) is Gradient layer texture, which is different from the structure of the pores (5) in the layer (3). scaffolding (1) in each layer with different densities of extract. is configured. In this way, the upper layer (2) imitates cartilage tissue. structure, while the substrate (3) has a microstructure that mimics bone tissue. has. The gradient layered scaffold (1), which is the subject of the invention, is implanted in the body. When the cellular activation is formed between the contact surfaces, new cells can treat the area of both cartilage and bone damage. is in the making.
Bulusta kullanilan yöntemler iki basamaktan olusmaktadir. Ilk basamak; gradyan katmanli doku iskelesinin (1) olusturulmasidir. Kitosan-mukus ve kitosan-slime olmak üzere iki farkli ekstrakt içerigine sahip gradyan katmanli doku iskelesi (1) üretilmistir. Ikinci basamak ise elde edilen gradyan katmanli doku iskelesine (1) kemik ve kikirdak hücrelerinin ekilmesi asamasidir. Slime yapisinin polimer matriks içerisinde kullanimi bulusun yenilikçi yönlerinden birisidir. Literatürde iki tip salyangoz salgisi oldugu ortaya konmustur. Mukus ve slime, ayak tabanindaki farkli lokalizasyonlardaki bezlerden salgilanmaktadir. The methods used in the invention consist of two steps. first digit; is the creation of the gradient layered scaffold (1). chitosan-mucus and Gradient layered with two different extract contents, chitosan-slime tissue scaffold (1) was produced. The second step is the gradient layer obtained. is the stage of planting bone and cartilage cells on the tissue scaffold (1). slime The use of its structure in the polymer matrix is one of the innovative aspects of the invention. is one. It has been revealed in the literature that there are two types of snail secretions. mucus and Slime is secreted from glands in different localizations on the soles of the feet.
Slime ayak tabanindaki bezler tarafindan üretilmektedir. Mukus salgisi ise salyangozun dorsal ve lateral ayak epitelinde bulunan bezler tarafindan üretilir ve içeriginde spesifik proteinler barindirdigi için daha adeziv özellik göstermektedir. Salyangoz salgilari içerisinde insan vücudu ile uyumlu birçok bilesen bulunmasi nedeni ile biyo-uyumluluk özelligi göstermektedir. Bu bilesenler arasinda; allontoin, kollajen, elastin, glikolik asit, glikozaminoglikan gibi moleküler yapilar yer almaktadir. Bu moleküler yapilar osteokondral hasarlarin onarimi için gereken ve vücut içerisinde de mevcut olan bilesenlerdir. Slime is produced by glands on the sole of the foot. If mucus secretion It is produced by glands in the dorsal and lateral foot epithelium of the snail. and more adhesive properties as it contains specific proteins shows. Many snail secretions are compatible with the human body. Due to the presence of components, it shows biocompatibility feature. This among the components; allontoin, collagen, elastin, glycolic acid, glycosaminoglycan such as molecular structures. These molecular structures are osteochondral They are components that are required for the repair of damages and are also present in the body.
Kitosan-mukus ve kitosan-slime olmak üzere üretilen iki farkli oranda ekstrakt içeren gradyan katmanli doku iskelesinde (1) alt katman (3) kemigi, üst katman (2) ise kikirdak yapisini taklit etmektedir. Gradyan katmanli doku iskelesinin (1) kemik ile temas ettigi yüzeydeki mukus ve slime orani, kikirdak ile temas ettigi yüzeydeki mukus ve slime oranina göre fazladir. Bunun sebebi kemik yapisinin kikirdak yapisina göre daha sert olmasidir. Anatomik yapiyi göz önüne alarak olusturulan bu oranla gardyan katmanli doku iskelesi (1) katmanlarinin temas Bulusun yenilikçi ve özgün degeri; elde edilen gradyan katmanli doku iskelesinin (1) kitosan-slime ve kitosan-mukus bilesenlerinden olusmasidir. Extract produced in two different ratios as chitosan-mucus and chitosan-slime Gradient layer scaffold containing (1) lower layer (3) bone, upper layer (2) mimics the cartilage structure. Gradient layer scaffold (1) The ratio of mucus and slime on the surface where it comes in contact with the bone, It is higher than the mucus and slime ratio on the surface. This is because of the bone structure It is harder than the cartilage structure. Considering the anatomical structure With this ratio created, the contact of the layers of the guard layer scaffold (1) The innovative and original value of the invention; texture with resulting gradient layer scaffold (1) consists of chitosan-slime and chitosan-mucus components.
Gelistirilen gradyan katmanli doku iskelesinin (1) her bir katmanin farkli yapisal ve mekanik özellikleri içerebilmesi, ayni zamanda farkli hücre yerlesme ve tutunmasina imkan saglayabilmesi, özgün biyoaktif ve biyouyumlu yapida bulunmasi en önemli özelligidir. Gradyan yapida olusturulmasinin sebebi; osteokondral hasarlarda bir yüzeyi kemik dokusuna diger yüzeyinin ise kikirdak dokusuna temas etmesidir. Bu temas yüzeyleri arasinda hücresel aktivasyonlar ile olusan yeni hücreler hem kikirdak hem de kemik hasarinin oldugu bölgeyi tedavi edici yapidadir. Gelistirilen biyoaktif, biyouyumlu gradyan katmanli doku iskelesi (1) kikirdak doku gelismesini gösteren temel biyobelirteçlerden GAG, Kolajen, COMP vb. kemik doku gelismesini gösteren temel biyobelirteçlerden ALP, Kolajen, Osteokalsin vb. ile incelenmis ve olumlu sonuçlar alinmistir. Different structural structures of each layer of the developed gradient layer scaffold (1) and mechanical properties, as well as different cell placement and with its unique bioactive and biocompatible structure is its most important feature. The reason for creating a gradient structure; In osteochondral injuries, one surface is bone tissue and the other surface is cartilage. touching the tissue. Cellular activations between these contact surfaces The new cells formed by the urethra form the area of both cartilage and bone damage. is therapeutic. Developed bioactive, biocompatible gradient layered tissue scaffold (1) GAG, which is one of the main biomarkers showing cartilage tissue development, Collagen, COMP etc. one of the main biomarkers showing bone tissue development ALP, Collagen, Osteocalcin etc. investigated and positive results were obtained.
Ayrica canlilik testleri ve toksisite testleri ile de yapilarin biyouyumlu oldugu gösterilebilmistir. Bununla birlikte gradyan katmanli doku iskelesinin (1) olusumunda kullanilan bütün bilesenler antimikrobiyal özelliklere sahiptir. Bu sebeple gradyan katmanli doku iskelesi (1) vücut içerisine implante edildiginde biyouyumluluk göstermekte ve ayni zamanda enfeksiyon olusumunu engelleyebilmektedir. In addition, it has been determined that the structures are biocompatible with viability tests and toxicity tests. can be displayed. However, the gradient layer scaffold (1) All the components used in its formation have antimicrobial properties. This Therefore, when the gradient layer scaffold (1) is implanted in the body, It shows biocompatibility and also prevents the formation of infection. can prevent.
Bulus konusu gradyan katmanli doku iskelesinin (1) üretiminde “freeze-drying” (liyofilizasyon) yöntemi kullanilmaktadir. “Freeze drying” yönteminin Türkçe karsiligi dondurarak kurutmadir. Yöntemde, ürün ilk olarak liyofilizatör (dondurarak kurutma cihazi) tarafindan dondurulmakta ve ardindan belirli bir basinç altinda üründe bulunan su moleküllerinin buharlasmasi saglanmaktadir. “freeze-drying” in the production of the gradient layer scaffold (1), which is the subject of the invention (lyophilization) method is used. Turkish version of the "freeze drying" method the opposite is freeze-drying. In the method, the product is first processed in the lyophilizer. (freeze drying device) and then a certain The evaporation of water molecules in the product is provided under pressure.
Böylece üründe gözenekli (5) yapilar elde edilebilmektedir. Thus, porous (5) structures can be obtained in the product.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2019/08115A TR201908115A2 (en) | 2019-05-28 | 2019-05-28 | BIOACTIVE TISSUE SCAFFOLDING WITH MUCUS AND SLIME BASED GRADIAN LAYER |
| PCT/TR2020/050409 WO2020242416A1 (en) | 2019-05-28 | 2020-05-09 | Gradient layered bioactive scaffold based on mucus and slime |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2019/08115A TR201908115A2 (en) | 2019-05-28 | 2019-05-28 | BIOACTIVE TISSUE SCAFFOLDING WITH MUCUS AND SLIME BASED GRADIAN LAYER |
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| TR201908115A2 true TR201908115A2 (en) | 2020-12-21 |
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| TR (1) | TR201908115A2 (en) |
| WO (1) | WO2020242416A1 (en) |
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| CN115634311A (en) * | 2022-09-27 | 2023-01-24 | 润原生物科技(苏州)有限公司 | Multi-structure cartilage repair implant and preparation method thereof |
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| EP0992251A1 (en) * | 1998-10-07 | 2000-04-12 | Isotis B.V. | Device for tissue engineering a bone equivalent |
| US20040078090A1 (en) * | 2002-10-18 | 2004-04-22 | Francois Binette | Biocompatible scaffolds with tissue fragments |
| US20060293760A1 (en) * | 2005-06-24 | 2006-12-28 | Dedeyne Patrick G | Soft tissue implants with improved interfaces |
| CN102935019B (en) * | 2012-10-19 | 2016-01-06 | 华中科技大学 | A kind of preparation method of the gradient lamination porous support based on microsphere selective laser sintering |
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