KR20240069643A - 3-Dimensional Biocompatible Structure for Regeneration of Body Vessel - Google Patents
3-Dimensional Biocompatible Structure for Regeneration of Body Vessel Download PDFInfo
- Publication number
- KR20240069643A KR20240069643A KR1020230154228A KR20230154228A KR20240069643A KR 20240069643 A KR20240069643 A KR 20240069643A KR 1020230154228 A KR1020230154228 A KR 1020230154228A KR 20230154228 A KR20230154228 A KR 20230154228A KR 20240069643 A KR20240069643 A KR 20240069643A
- Authority
- KR
- South Korea
- Prior art keywords
- present
- poly
- regeneration
- phloem
- lymphatic
- Prior art date
Links
- 230000008929 regeneration Effects 0.000 title claims abstract description 23
- 238000011069 regeneration method Methods 0.000 title claims abstract description 23
- 210000001365 lymphatic vessel Anatomy 0.000 claims abstract description 36
- 239000007943 implant Substances 0.000 claims abstract description 24
- 206010025282 Lymphoedema Diseases 0.000 claims abstract description 17
- 210000001124 body fluid Anatomy 0.000 claims abstract description 17
- 239000010839 body fluid Substances 0.000 claims abstract description 17
- 208000002502 lymphedema Diseases 0.000 claims abstract description 17
- 210000004204 blood vessel Anatomy 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 12
- 230000001939 inductive effect Effects 0.000 claims abstract description 8
- 208000023589 ischemic disease Diseases 0.000 claims abstract description 8
- 239000012530 fluid Substances 0.000 claims abstract description 5
- -1 poly(caprolactone) Polymers 0.000 claims description 45
- 210000004880 lymph fluid Anatomy 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 229920001610 polycaprolactone Polymers 0.000 claims description 9
- 229920000117 poly(dioxanone) Polymers 0.000 claims description 7
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 5
- 229920002988 biodegradable polymer Polymers 0.000 claims description 5
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 229940065514 poly(lactide) Drugs 0.000 claims description 4
- 239000004621 biodegradable polymer Substances 0.000 claims description 3
- 230000037361 pathway Effects 0.000 claims description 3
- 230000003966 vascular damage Effects 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 abstract description 20
- 238000011282 treatment Methods 0.000 abstract description 9
- 230000009471 action Effects 0.000 abstract description 6
- 230000001926 lymphatic effect Effects 0.000 abstract description 5
- 230000001575 pathological effect Effects 0.000 abstract description 5
- 210000002751 lymph Anatomy 0.000 abstract description 4
- 230000017531 blood circulation Effects 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
- 230000003902 lesion Effects 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 210000001165 lymph node Anatomy 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 210000005073 lymphatic endothelial cell Anatomy 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 7
- 101710178181 Lymphatic vessel endothelial hyaluronic acid receptor 1 Proteins 0.000 description 6
- 102100026849 Lymphatic vessel endothelial hyaluronic acid receptor 1 Human genes 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 230000006378 damage Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 5
- 229960004657 indocyanine green Drugs 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 206010010356 Congenital anomaly Diseases 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000009547 development abnormality Effects 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 238000003125 immunofluorescent labeling Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 210000003563 lymphoid tissue Anatomy 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 210000004872 soft tissue Anatomy 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 230000007998 vessel formation Effects 0.000 description 3
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 208000015695 Primary lymphedema Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229920000249 biocompatible polymer Polymers 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- 230000003692 lymphatic flow Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011555 rabbit model Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- 238000010146 3D printing Methods 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102100026735 Coagulation factor VIII Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 229930188620 butyrolactone Natural products 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 210000001698 popliteal fossa Anatomy 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
Classifications
-
- 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
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- A61L2430/22—Materials or treatment for tissue regeneration for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials For Medical Uses (AREA)
Abstract
본 발명은 체관 재생 유도용 인체 삽입물 및 이를 이용한 림프부종(lymphedema) 또는 허혈성 질환의 치료 방법에 관한 것이다. 본 발명의 구조체는 적절한 물리적 강도와 기계적 지지(support)를 제공함으로써 림프관 또는 혈관 등의 체관이 재생되는 동안 이의 재손상을 방지할 뿐 아니라, 요철(예를 들어 H 형강) 또는 내강(예를 들어 관 형태)을 가지는 간단한 막대 구조를 이용하여 모세관 현상을 통한 체액의 유동을 촉진함으로써 생체 내 체관 조직을 구조적, 기능적으로 모사한다. 아울러, 본 발명의 구조체는 병변부에 이식된 뒤 체관 재생 완료 후 적절한 시기에 분해됨으로써, 림프액의 유동 차단 또는 혈류의 감소로 인해 발생하는 다양한 병적 상태에 대한 효율적인 치료 수단으로 유용하게 이용될 수 있다. The present invention relates to a human implant for inducing phloem regeneration and a method of treating lymphedema or ischemic disease using the same. The structure of the present invention not only prevents re-damage of phloem tubes such as lymph vessels or blood vessels during regeneration by providing appropriate physical strength and mechanical support, but also prevents re-damage of phloem tubes such as lymphatic vessels or blood vessels by providing appropriate physical strength and mechanical support. It structurally and functionally mimics in vivo phloem tissue by promoting the flow of body fluids through capillary action using a simple rod structure (in the form of a tube). In addition, the structure of the present invention is decomposed at an appropriate time after completion of phloem regeneration after being transplanted to the lesion area, so it can be usefully used as an efficient treatment method for various pathological conditions caused by blockage of lymphatic fluid flow or reduction of blood flow. .
Description
본 발명은 모세관 현상을 통해 체액의 유동을 촉진하는 막대 형상의 생체 적합성 구조체와, 이를 이용한 체관 재생 유도 방법에 관한 것이다.The present invention relates to a rod-shaped biocompatible structure that promotes the flow of body fluid through capillary action and a method of inducing phloem regeneration using the same.
림프부종(lymphedema)이란 림프계 손상으로 조직 속 림프액이 연부조직 사이질에 비정상적으로 고이는 난치성 만성질환을 의미한다. 림프부종의 원인으로는 유전적 요인(1차성 림프부종), 감염, 암, 외상성 손상(1차성 림프부종) 등이 있다. 특히 암 치료 과정에서 림프절 및 림프관이 파괴되어 암환자에게서 림프부종의 발병이 종종 관찰된다. 림프부종이 심해질 경우 면역반응이 정상적으로 이뤄지지 않아 작은 상처에도 쉽게 감염이 발생하고 봉와직염 및 패혈증과 같은 합병증으로 생명이 위협받을 수 있다.Lymphedema refers to an incurable chronic disease in which lymph fluid in tissues abnormally accumulates in the interstitium of soft tissues due to damage to the lymphatic system. Causes of lymphedema include genetic factors (primary lymphedema), infection, cancer, and traumatic injury (primary lymphedema). In particular, the development of lymphedema is often observed in cancer patients as lymph nodes and lymphatic vessels are destroyed during cancer treatment. If lymphedema becomes severe, the immune response does not occur normally, causing infection even in small wounds and life-threatening complications such as cellulitis and sepsis.
림프부종의 증상으로는 팔, 다리 등의 국소 말단 부위에서부터 전신적인 신체 부종 및 이와 동반하는 통증, 손발 저림, 경화증 등이 있다. 일단 증상이 발생하면 지속적으로 진행되는 만성 질환으로 현재까지는 근본적인 치료가 어려운 난치성 질환에 속한다. Symptoms of lymphedema include systemic swelling of the body, from local extremities such as arms and legs, and accompanying pain, numbness in the hands and feet, and sclerosis. Once symptoms occur, it is a chronic disease that continues to progress and is currently an incurable disease that is difficult to fundamentally treat.
림프부종 환자는 매년 증가하는 양상으로 국내 환자수는 2017년 2만 999명에서 2021년 3만 4,025명으로 무려 62%가 증가했다. 특히 유방암에 걸린 후 높은 발병 빈도를 보이는 만큼 전체 환자의 74% 이상이 여성 환자로 관찰된다. 이렇듯 국내에서 매년 유병률이 증가하고 있지만, 현재로는 보존요법으로 압박 및 물리치료가, 외과적 치료로는 림프정맥문합술, 림프절전이술, 림프절 절제술 등이 시행되고 있으나 수술 치료 이후에도 50% 내외의 환자에서만 증상이 호전되는 등 치료 효과가 제한적이며 완치가 어렵다는 한계점이 존재한다. 이에, 림프부종의 근본적인 병인의 제거를 위해 손상된 림프절 및 림프관을 효율적으로 재생하는 재생의료기술기반의 새로운 치료법 개발이 요구되고 있다.The number of patients with lymphedema increases every year, with the number of domestic patients increasing by a whopping 62% from 20,999 in 2017 to 34,025 in 2021. In particular, as it shows a high incidence after breast cancer, more than 74% of all patients are observed to be female. As such, the prevalence rate is increasing every year in Korea, but currently, compression and physical therapy are used as conservative treatments, and lymphovenous anastomosis, lymph node metastasis, and lymph node dissection are used as surgical treatments. However, even after surgical treatment, approximately 50% of patients suffer from the disease. There are limitations in that treatment effectiveness is limited, with symptoms improving only in certain cases, and complete cure is difficult. Accordingly, there is a need to develop new treatments based on regenerative medicine technology that efficiently regenerate damaged lymph nodes and lymphatic vessels in order to eliminate the fundamental cause of lymphedema.
본 명세서 전체에 걸쳐 다수의 논문 및 특허 문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허 문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되었다. 이로 인해 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다. Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety. As a result, the level of technical field to which the present invention belongs and the content of the present invention are explained more clearly.
본 발명자들은 수술, 외상, 암, 감염 또는 선천적 발달 이상 등의 다양한 원인에 의해 구조적, 기능적으로 손상된 체관(body vessel), 예를 들어 림프관 또는 혈관 조직을 효율적으로 복구할 수 있는 조직 재생용 인체 삽입 구조체를 개발하기 위하여 예의 연구 노력하였다. 그 결과, 막대 형상의 생분해성 구조체로서 그 횡단면이 체액, 구체적으로는 림프액 또는 혈액이 흘러갈 수 있는 폐쇄된 통로 역할을 하는 내강, 개방된 통로 역할을 하는 요철 또는 이들의 조합을 가지는 구조체를 체관 손상 부위에 이식할 경우 단기적으로 뼈대로서의 역할을 통해 기계적 지지(mechanical support)를 제공하면서 모세관 현상을 통해 체액의 원활한 유동을 촉진하고 혈관, 림프절 또는 림프관의 재생을 유도함으로써 혈액 누수, 허혈성 질환, 림프부종을 비롯하여 혈관 또는 림프관 손상을 원인으로 하는 다양한 병적 상태를 효율적으로 개선 및 치료할 수 있음을 발견함으로써, 본 발명을 완성하게 되었다.The present inventors have proposed a human implant for tissue regeneration that can efficiently restore structurally and functionally damaged body vessels, such as lymphatic vessels or vascular tissue, due to various causes such as surgery, trauma, cancer, infection, or congenital developmental abnormalities. Extensive research efforts were made to develop the structure. As a result, a sieve tube is a rod-shaped biodegradable structure whose cross-section has a lumen that serves as a closed passage through which body fluids, specifically lymph fluid or blood, can flow, irregularities that serve as open passages, or a combination thereof. When transplanted to a damaged area, it acts as a framework in the short term to provide mechanical support, promotes smooth flow of body fluids through capillary action, and induces regeneration of blood vessels, lymph nodes, or lymphatic vessels, thereby preventing blood leakage, ischemic disease, and lymphatic drainage. The present invention was completed by discovering that various pathological conditions caused by damage to blood vessels or lymphatic vessels, including edema, can be efficiently improved and treated.
따라서 본 발명의 목적은 체관 재생 유도용 인체 삽입물 및 이를 포함하는 림프부종(lymphedema) 또는 허혈성 질환 치료용 조성물을 제공하는 데 있다.Therefore, the purpose of the present invention is to provide a human implant for inducing phloem regeneration and a composition containing the same for treating lymphedema or ischemic disease.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become clearer from the following detailed description, claims, and drawings.
본 발명의 일 양태에 따르면, 본 발명은 막대 형상의 생분해성 구조체를 포함하고, 상기 구조체의 횡단면은 체액(body fluid)의 유로(fluid pathway)를 제공하는 하나 이상의 요철, 내강(cavity) 또는 이들의 조합을 포함하는, 체관(body vessel) 재생 유도용 인체 삽입물을 제공한다.According to one aspect of the present invention, the present invention includes a rod-shaped biodegradable structure, and the cross-section of the structure has one or more irregularities, cavities, or these that provide a fluid pathway for body fluid. Provided is a human body insert for inducing phloem (body vessel) regeneration, comprising a combination of the following.
본 발명자들은 수술, 외상, 암, 감염 또는 선천적 발달 이상 등의 다양한 원인에 의해 구조적, 기능적으로 손상된 체관(body vessel), 예를 들어 림프관 또는 혈관 조직을 효율적으로 복구할 수 있는 조직 재생용 인체 삽입 구조체를 개발하기 위하여 예의 연구 노력하였다. 그 결과, 막대 형상의 생분해성 구조체로서 그 횡단면이 체액, 구체적으로는 림프액 또는 혈액이 흘러갈 수 있는 폐쇄된 통로 역할을 하는 내강, 개방된 통로 역할을 하는 요철 또는 이들의 조합을 가지는 구조체를 체관 손상 부위에 이식할 경우 단기적으로 뼈대로의 역할을 통해 기계적 지지를 제공하면서 모세관 현상을 통해 체액의 원활한 유동을 촉진하고 혈관, 림프절 또는 림프관의 재생을 유도함으로써 혈액 누수, 허혈성 질환, 림프부종을 비롯하여 혈관 또는 림프관 손상을 원인으로 하는 다양한 병적 상태를 효율적으로 개선 및 치료할 수 있음을 발견하였다. The present inventors have proposed a human implant for tissue regeneration that can efficiently restore structurally and functionally damaged body vessels, such as lymphatic vessels or vascular tissue, due to various causes such as surgery, trauma, cancer, infection, or congenital developmental abnormalities. Extensive research efforts were made to develop the structure. As a result, a sieve tube is a rod-shaped biodegradable structure whose cross-section has a lumen that serves as a closed passage through which body fluids, specifically lymph fluid or blood, can flow, irregularities that serve as open passages, or a combination thereof. When transplanted to a damaged area, it acts as a framework in the short term to provide mechanical support, promotes smooth flow of body fluids through capillary action, and induces regeneration of blood vessels, lymph nodes, or lymphatic vessels, thereby preventing blood leakage, ischemic disease, lymphedema, etc. It was discovered that various pathological conditions caused by damage to blood vessels or lymphatic vessels can be efficiently improved and treated.
본 명세서에서 용어“체관(body vessel)”은 체액의 이동 경로를 제공하는 관 형태(tube-shaped)의 여하한 체내 내강(passage lumen) 조직을 포괄하는 의미로서, 림프관, 혈관, 담관(bile duct) 및 요도관(urethral passage)을 포함하나, 이제 제한되는 것은 아니다. 보다 구체적으로는, 본 발명의 삽입물로 재생될 수 있는 체관은 혈관 또는 림프관이다. As used herein, the term “body vessel” refers to any tube-shaped passage lumen tissue in the body that provides a movement path for body fluids, including lymph vessels, blood vessels, and bile ducts. ) and urethral passage, but are not limited to this. More specifically, the phloem tubes that can be regenerated with the insert of the present invention are blood vessels or lymphatic vessels.
본 명세서에서 용어“구조체”는 생체 세포, 구체적으로는 손상된 체관에서 유래한 세포 또는 이의 회복 또는 재생에 관여하는 세포(예를 들어 줄기세포)를 안착시켜 조직의 회복 및 재생을 촉진하면서, 회복기간 동안 기계적 지지를 제공하여 체관의 재손상을 방지하고, 체액의 유동로를 제공함으로써 체관 조직의 일시적 모사체(temporary mimetic) 역할을 하는 조직공학(tissue engineering)적 구조체를 의미한다. As used herein, the term “structure” refers to the installation of biological cells, specifically cells derived from damaged phloem, or cells involved in their recovery or regeneration (e.g. stem cells), thereby promoting tissue recovery and regeneration, and during the recovery period. It refers to a tissue engineering structure that serves as a temporary mimetic of phloem tissue by providing mechanical support to prevent re-damage of the phloem tube and providing a flow path for body fluids.
용어“세포의 안착(cell attachment)”은 세포가 고유의 생물학적 활성을 유지한 채 기질 또는 다른 세포에 직접 또는 간접적으로 흡착하는 것을 의미한다. The term “cell attachment” refers to the direct or indirect adsorption of cells to a substrate or other cells while maintaining their original biological activity.
본 명세서에서 용어“이식”은 수용자에게 이식된 지지체, 조직 또는 세포의 기능적 완전성을 유지하려는 목적 하에 공여자로부터 수용자에게 생존 조직, 조직 모사체, 세포, 조직 재생을 돕는 유효성분 또는 이들을 수용하는 인공 구조체를 전달하는 과정을 의미한다. 따라서, 용어 “이식”또는“이식물”은“삽입”또는“삽입물”과 동일한 의미를 가진다.As used herein, the term “transplant” refers to a viable tissue, tissue mimic, cell, active ingredient that aids tissue regeneration, or an artificial structure that receives them from a donor to a recipient with the purpose of maintaining the functional integrity of the scaffold, tissue, or cells transplanted into the recipient. refers to the process of delivering. Accordingly, the terms “implant” or “implant” have the same meaning as “implant” or “implant”.
본 명세서에서 용어“생분해성”은 pH 6-8의 생리적 용액(physiological solution)에 노출되었을 때 자연적으로 분해되는 성질을 의미하며, 구체적으로는 생체 내에서 체액, 분해 효소 또는 미생물 등에 의해서 시간의 경과에 따라 분해될 수 있는 성질을 의미한다. As used herein, the term “biodegradability” refers to the property of being naturally decomposed when exposed to a physiological solution of pH 6-8, and specifically, over time by body fluids, decomposition enzymes, or microorganisms in vivo. It means the property of being able to be decomposed according to .
본 명세서에서 용어“요철”은 함몰부 및/또는 돌출부가 규칙적 또는 불규칙적으로 교차하면서 표면에 홈이 형성되는 구조를 의미한다. 이와 같이 형성된 홈은 개방된 유로(fluid pathway) 역할을 하여 모세관 현상을 통해 림프액의 유동을 야기할 수 있다. As used herein, the term “irregularity” refers to a structure in which depressions and/or protrusions intersect regularly or irregularly to form grooves on the surface. The groove formed in this way can serve as an open fluid pathway and cause the flow of lymph fluid through capillary action.
본 발명의 구체적인 구현예에 따르면, 상기 요철을 포함하는 횡단면은 H 형강(H-beam)의 횡단면이다. 본 명세서에서 용어“H 형강”은 횡단면이 알파벳 H의 형태인 막대형 구조체를 의미한다.According to a specific embodiment of the present invention, the cross section including the irregularities is a cross section of an H-beam. As used herein, the term “H-beam” refers to a bar-shaped structure whose cross-section is in the shape of the letter H.
본 발명의 구체적인 구현예에 따르면, 상기 요철을 포함하는 횡단면은 방사형(radial)의 횡단면이다. 본 명세서에서 용어“방사형”은 중심점으로부터 주변부로 복수의 돌출부가 대칭 또는 비대칭 형태로 바퀴살 모양으로 뻗어 나간 형상을 의미한다. 여기서 바퀴살 모양으로 뻗어나간 돌출부와 인접 돌출부 사이에 형성된 공간은 개방된 유로 역할을 하는 홈이 된다. According to a specific embodiment of the present invention, the cross section including the irregularities is a radial cross section. In this specification, the term “radial” refers to a shape in which a plurality of protrusions extend from the center point to the periphery in a symmetrical or asymmetrical shape in the shape of spokes. Here, the space formed between the protrusion extending in the shape of a wheel spoke and the adjacent protrusion becomes a groove that serves as an open flow path.
본 발명에서 이용되는 막대 형상의 생분해성 구조체는 복수의 구조체가 서로 꼬여 트위스트 또는 브레이드를 이룬 형태로 적용될 수 있다.The rod-shaped biodegradable structure used in the present invention may be applied in the form of a plurality of structures twisted or braided together.
본 명세서에서 용어“트위스트”는 두 가닥 이상의 막대 형상의 구조체가 동일한 회전 방향으로 꼬인 형상을 의미한다. As used herein, the term “twist” refers to a shape in which two or more rod-shaped structures are twisted in the same direction of rotation.
본 명세서에서 용어 “브레이드”는 세 가닥 이상의 막대 형상의 구조체 중 두 가닥 이상이 교차하여 꼬인 형상을 의미한다. As used herein, the term “braid” refers to a twisted shape in which two or more strands of a rod-shaped structure of three or more strands intersect.
보다 구체적으로는, 상기 복수의 돌출부는 중심점에 대한 점대칭 관계에 있다.More specifically, the plurality of protrusions are in a point-symmetrical relationship with respect to the central point.
본 발명의 구체적인 구현예에 따르면, 상기 내강의 단면 형상은 원형 또는 다각형이다. According to a specific embodiment of the present invention, the cross-sectional shape of the lumen is circular or polygonal.
본 발명의 구조체가 내강을 가지는 경우, 상기 내강은 림프액이 흘러갈 수 있는 폐쇄된 유로 역할을 한다. 상기 내강이 원형일 경우 이는 기하학적으로 완전한 원형일 필요는 없으며 원형과 유사한 곡면을 가질 수 있다. 상기 내강이 다각형인 경우, 예를 들어 삼각형, 사각형, 오각형, 또는 육각형일 수 있으나, 이에 제한되는 것은 아니다. 이들 다각형은 정다각형일 수도 있고 아닐 수도 있다. 구체적인 일 구현예에 따르면, 상기 다각형의 내강은 직사각형 또는 정사각형의 단면 형상을 가진다. When the structure of the present invention has a lumen, the lumen serves as a closed channel through which lymph fluid can flow. When the lumen is circular, it need not be geometrically perfectly circular and may have a curved surface similar to a circular shape. If the lumen is polygonal, for example, it may be a triangle, square, pentagon, or hexagon, but is not limited thereto. These polygons may or may not be regular polygons. According to one specific embodiment, the polygonal lumen has a rectangular or square cross-sectional shape.
본 발명에 따르면, 본 발명의 구조체는 전술한 요철 또는 내강이 택일적으로 적용된 횡단면을 가질 수도 있고, 또는 요철과 내강이 모두 적용된 횡단면을 가질 수도 있다. 요철과 내강이 모두 적용된 경우, 요철을 형성하는 돌출부의 방사상 중심과 내강의 중심은 일치할 수도 있고 일치하지 않을 수도 있다. 보다 구체적으로는, 돌출부의 방사상과 내강은 동일한 중심을 가진다. According to the present invention, the structure of the present invention may have a cross section to which the above-mentioned irregularities or lumens are alternatively applied, or it may have a cross section to which both the irregularities and lumens are applied. When both the convexity and the lumen are applied, the radial center of the protrusion forming the convexity and the center of the lumen may or may not coincide. More specifically, the radial and lumen of the protrusion have the same center.
본 발명의 구체적인 구현예에 따르면, 본 발명의 막대 형상의 생분해성 구조체의 횡단면은 0.1 - 3.0 mm의 장축과 0.1 - 3.0 mm의 단축을 가진다. 장축 또는 단축이 0.1 mm 미만인 경우 요철에 의한 홈의 크기가 혈관 내피세포 또는 림프 내피세포 형성에 적합하지 않고, 3.0 mm 초과인 경우 구조체의 높은 강성으로 인하여 환자에게 강한 통증을 유발하게 된다. 보다 구체적으로는 0.5 - 1.5 mm의 장축과 0.5 - 1.5 mm의 단축을 가지며, 가장 구체적으로는 0.8 - 1.2 mm의 장축과 0.6 - 0.8 mm의 단축을 가진다. According to a specific embodiment of the present invention, the cross-section of the rod-shaped biodegradable structure of the present invention has a major axis of 0.1 - 3.0 mm and a minor axis of 0.1 - 3.0 mm. If the long axis or short axis is less than 0.1 mm, the size of the groove due to the irregularities is not suitable for forming vascular endothelial cells or lymphatic endothelial cells, and if it is more than 3.0 mm, it causes strong pain to the patient due to the high rigidity of the structure. More specifically, it has a major axis of 0.5 - 1.5 mm and a minor axis of 0.5 - 1.5 mm, and most specifically, it has a major axis of 0.8 - 1.2 mm and a minor axis of 0.6 - 0.8 mm.
본 발명의 구체적인 구현예에 따르면, 상기 내강의 면적은 0.0025 - 6.25 mm2 이다. 보다 구체적으로는 0.01 - 4.0 mm2 이며, 보다 더 구체적으로는 0.1 - 0.5 mm2 이고, 보다 더 구체적으로는 0.1 - 0.3 mm2이며, 가장 구체적으로는 0.1 - 0.2 mm2이다.According to a specific embodiment of the present invention, the area of the lumen is 0.0025 - 6.25 mm 2 . More specifically, it is 0.01 - 4.0 mm 2 , even more specifically it is 0.1 - 0.5 mm 2 , even more specifically it is 0.1 - 0.3 mm 2 , and most specifically it is 0.1 - 0.2 mm 2 .
본 발명의 구체적인 구현예에 따르면, 본 발명의 생분해성 구조체는 생분해성 고분자를 포함한다.According to a specific embodiment of the present invention, the biodegradable structure of the present invention includes a biodegradable polymer.
본 명세서에서 용어“고분자”는 동일하거나 상이한 종류의 단량체가 연속적으로 결합된 합성 또는 천연 고분자 화합물을 지칭한다. 따라서, 고분자에는 단독 중합체(한 종류의 단량체가 중합화된 중합체)와 적어도 2종의 상이한 단량체의 중합에 의해 제조된 혼성중합체를 포함되며, 혼성중합체에는 공중합체(2종의 상이한 단량체로부터 제조된 중합체)와 2종 초과의 상이한 단량체로부터 제조된 중합체를 모두 포함한다. 본 발명에 따르면, 본 발명의 생분해성 구조체는 생분해성 또는 생체적합성 고분자를 원료로 하여 제조된 구조체일 수 있다.As used herein, the term “polymer” refers to a synthetic or natural polymer compound in which the same or different types of monomers are sequentially bonded. Accordingly, polymers include homopolymers (polymers made from one type of monomer) and interpolymers made by polymerizing at least two different monomers, and interpolymers include copolymers (polymers made from two different monomers). polymers) and polymers prepared from more than two different monomers. According to the present invention, the biodegradable structure of the present invention may be a structure manufactured using a biodegradable or biocompatible polymer as a raw material.
본 명세서에서 용어“생체적합성”은 생체 내에 투여되어 기관의 세포, 조직 또는 체액과 접촉하는 경우 단기적 혹은 장기적 부작용을 일으키지 않는 성질을 의미하며, 구체적으로는 생체조직 또는 혈액과 접촉하여 조직을 괴사시키거나 혈액을 응고시키지 않는 조직적합성(tissue compatibility) 및 항응혈성(blood compatibility) 뿐 아니라 생체 투여 후 일정 기간이 경과한 뒤 소멸되는 생분해성(biodegradability)을 포함하는 의미이다.As used herein, the term “biocompatibility” refers to the property of not causing short-term or long-term side effects when administered in the body and in contact with cells, tissues, or body fluids of an organ. Specifically, it refers to the property of not causing tissue necrosis upon contact with living tissue or blood. This includes not only tissue compatibility and anticoagulant properties, which do not coagulate blood, but also biodegradability, which disappears after a certain period of time after administration to the body.
본 발명의 생분해성 구조체의 원료로 사용될 수 있는 생분해성 또는 생체적합성 고분자는 PCL[poly(caprolactone)], HEMA[poly(2-hydroxyethyl metacrylate)], PVA(polyvinylalcohol, PEO(Polyethyleneoxide), phospholipid, collagen, alipatic polyether, PLA[poly(lactide)], PGA[poly(glycolide)], PDO[poly(dioxanone)]), PBL[poly(butyrolactone)], PVL[poly(valerolactone)], PLGA[poly(lactide-co-glycolide)], PU(polyurethane), fibronectin, vitronectin, poly(L-lysin), poly(L-glutamic acid), Poly(aspartic acid), carboxymethyl cellulose, cellulose sulfate, agarose, alginate, carrangeenan, hyaluronic acid, dextran, chitosan, poly(hydroxybutyric acid), poly(alkylene succinate), polyamide, poly(anhydride), poly(ortho-ester), poly(cyano acrylates), polyphosphazene, poly(hydroxyethyl metacrylate), poly(methyl metacrylate), poly(tetrafluoroethylene), poly(dimethylsiloxane), poly(ethyleneoxide-β-propyleneoxide), Poly(vinylmethylether), Poly(N-alkylacrylamide), decelluarized matrix (dECM) 및 이들의 조합을 포함하나, 이에 제한되는 것은 아니다. 보다 구체적으로는, 본 발명에서 이용되는 생분해성 고분자는 PCL[poly(caprolactone)], PLA[poly(lactide)], PGA[poly(glycolide)], PDO[poly(dioxanone)]), PBL[poly(butyrolactone)], PVL[poly(valerolactone)] 및 PLGA[poly(lactide-co-glycolide)]로 구성된 군으로부터 선택되는 하나 이상이다.Biodegradable or biocompatible polymers that can be used as raw materials for the biodegradable structure of the present invention include PCL [poly(caprolactone)], HEMA [poly(2-hydroxyethyl methacrylate)], PVA (polyvinylalcohol, PEO (Polyethyleneoxide), phospholipid, and collagen. , alipatic polyether, PLA[poly(lactide)], PGA[poly(glycolide)], PDO[poly(dioxanone)]), PBL[poly(butyrolactone)], PVL[poly(valerolactone)], PLGA[poly(lactide)] -co-glycolide)], PU(polyurethane), fibronectin, vitronectin, poly(L-lysin), poly(L-glutamic acid), Poly(aspartic acid), carboxymethyl cellulose, cellulose sulfate, agarose, alginate, carrangeenan, hyaluronic acid, dextran, chitosan, poly(hydroxybutyric acid), poly(alkylene succinate), polyamide, poly(anhydride), poly(ortho-ester), poly(cyano acrylates), polyphosphazene, poly(hydroxyethyl methacrylate), poly(methyl methacrylate) ), poly(tetrafluoroethylene), poly(dimethylsiloxane), poly(ethyleneoxide-β-propyleneoxide), Poly(vinylmethylether), Poly(N-alkylacrylamide), decelluarized matrix (dECM), and combinations thereof. no. More specifically, the biodegradable polymers used in the present invention are PCL[poly(caprolactone)], PLA[poly(lactide)], PGA[poly(glycolide)], PDO[poly(dioxanone)]), and PBL[poly(dioxanone)]). (butyrolactone)], PVL [poly(valerolactone)], and PLGA [poly(lactide-co-glycolide)].
본 발명의 구체적인 구현예에 따르면, 상기 체액은 림프액이며, 상기 체관은 림프관이다.According to a specific embodiment of the present invention, the body fluid is lymph fluid, and the sieve tube is a lymphatic vessel.
본 발명의 구체적인 구현예에 따르면, 상기 체액은 혈액이며, 상기 체관은 혈관이다.According to a specific embodiment of the present invention, the body fluid is blood, and the phloem tube is a blood vessel.
본 발명의 다른 양태에 따르면, 본 발명은 전술한 본 발명의 인체 삽입물을 유효성분으로 포함하는 림프부종 치료용 조성물을 제공한다.According to another aspect of the present invention, the present invention provides a composition for treating lymphedema comprising the above-described human implant of the present invention as an active ingredient.
본 발명의 또 다른 양태에 따르면, 본 발명은 전술한 본 발명의 인체 삽입물을 대상체의 체내에 삽입하는 단계를 포함하는 림프부종의 치료 방법을 제공한다.According to another aspect of the present invention, the present invention provides a method of treating lymphedema comprising inserting the above-described human implant of the present invention into the body of a subject.
본 명세서에서 용어“림프부종(lymphedema)”은 수술, 외상, 암, 감염 또는 선천적 발달 이상 등의 다양한 원인에 의해 림프관 조직이 손상받음으로서 림프액의 이동이 원활하지 못하게 되고, 이동이 차단된 림프액이 피부와 피하 등 연부조직 사이질에 과다하게 축적되어 팔 또는 다리 등의 부피가 비정상적으로 확장되는 질환을 의미한다.In this specification, the term “lymphedema” refers to damage to the lymphatic tissue due to various causes such as surgery, trauma, cancer, infection, or congenital developmental abnormalities, resulting in poor movement of lymph fluid and lymph fluid whose movement is blocked. It refers to a disease in which excessive accumulation occurs in the interstitium of soft tissues such as the skin and subcutaneous tissue, resulting in abnormal expansion of the volume of the arms or legs.
본 명세서에서 용어“치료”는 (a) 질환, 질병 또는 증상의 발전의 억제; (b) 질환, 질병 또는 증상의 경감; 또는 (c) 질환, 질병 또는 증상을 제거하는 것을 의미한다. 본 발명의 조성물을 대상체의 병변부에 이식하면 순환되지 못하고 특정 연부조직에 축적된 림프액의 원활한 유동을 촉진하고 손상된 림프관과 림프절의 재생을 유도함으로써 림프관 조직의 손상 및 기능 부전을 원인으로 하는 일련의 증상의 발전을 억제하거나, 이를 제거하거나 또는 경감시키는 역할을 한다. 따라서, 본 발명의 조성물은 그 자체로 이들 질환 치료의 조성물이 될 수도 있고, 혹은 다른 약리성분(예를 들어 림프관 조직으로 분화할 수 있는 줄기세포)의 투여와 함께 이식되어 림프부종에 대한 치료 보조수단으로 적용될 수도 있다. 이에, 본 명세서에서 용어“치료”또는“치료제”는“치료 보조”또는“치료 보조제”의 의미를 포함한다. As used herein, the term “treatment” refers to (a) inhibiting the development of a disease, condition or symptom; (b) alleviation of a disease, condition or symptom; or (c) means eliminating a disease, condition or symptom. When the composition of the present invention is implanted into the lesion area of a subject, it promotes the smooth flow of lymph fluid that is not circulating and accumulated in specific soft tissues and induces regeneration of damaged lymphatic vessels and lymph nodes, thereby preventing a series of diseases caused by damage and dysfunction of lymphatic tissue. It plays a role in suppressing the development of symptoms, eliminating them, or alleviating them. Therefore, the composition of the present invention may itself be a composition for treating these diseases, or may be transplanted together with the administration of other pharmacological ingredients (e.g., stem cells capable of differentiating into lymphatic tissue) to assist in the treatment of lymphedema. It can also be applied as a means. Accordingly, in this specification, the term “treatment” or “therapeutic agent” includes the meaning of “therapeutic aid” or “therapeutic aid.”
본 명세서에서 용어“대상체”는 제한없이 인간, 마우스, 래트, 기니아 피그, 개, 토끼, 고양이, 말, 소, 돼지, 원숭이, 침팬지, 비비 또는 붉은털 원숭이를 포함한다. 구체적으로는, 본 발명의 대상체는 인간이다. As used herein, the term “subject” includes, without limitation, humans, mice, rats, guinea pigs, dogs, rabbits, cats, horses, cows, pigs, monkeys, chimpanzees, baboons, or rhesus monkeys. Specifically, the subject of the present invention is a human.
본 발명의 또 다른 양태에 따르면, 본 발명은 전술한 본 발명의 인체 삽입물을 유효성분으로 포함하는 혈관 누수 또는 혈관 손상으로 인한 허혈성 질환 치료용 조성물을 제공한다.According to another aspect of the present invention, the present invention provides a composition for treating ischemic disease caused by vascular leakage or vascular damage, comprising the above-described human implant of the present invention as an active ingredient.
본 발명의 또 다른 양태에 따르면, 본 발명은 전술한 본 발명의 인체 삽입물을 대상체의 체내에 삽입하는 단계를 포함하는 혈관 누수 또는 혈관 손상으로 인한 허혈성 질환의 치료 방법을 제공한다.According to another aspect of the present invention, the present invention provides a method of treating ischemic disease caused by vascular leakage or vascular damage, comprising inserting the above-described human implant of the present invention into the body of a subject.
본 발명에 따르면, 본 발명의 조성물이 손상된 혈관 병변부에 이식되면 혈관벽을 안정화하여 혈액의 누수를 막고 정상적인 혈관의 재생 및 성장을 촉진하여 허혈성 조직의 부종, 국소빈혈 및 허혈성 조직 괴사를 포함하여 혈류 감소로 인한 다양한 병적 상태를 효율적으로 치료할 수 있다.According to the present invention, when the composition of the present invention is implanted into a damaged vascular lesion, it stabilizes the blood vessel wall, prevents blood leakage, promotes the regeneration and growth of normal blood vessels, and improves blood flow, including ischemic tissue edema, ischemia, and ischemic tissue necrosis. Various pathological conditions caused by reduction can be efficiently treated.
본 발명의 특징 및 이점을 요약하면 다음과 같다:The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 체관 재생 유도용 인체 삽입물 및 이를 이용한 림프부종(lymphedema) 또는 허혈성 질환의 치료 방법을 제공한다.(a) The present invention provides a human implant for inducing phloem regeneration and a method of treating lymphedema or ischemic disease using the same.
(b) 본 발명의 구조체는 적절한 물리적 강도와 기계적 지지(support)를 제공함으로써 림프관 또는 혈관 등의 체관이 재생되는 동안 이의 재손상을 방지할 뿐 아니라, 요철(예를 들어 H 형강) 또는 내강(예를 들어 관 형태)을 가지는 간단한 막대 구조를 이용하여 모세관 현상을 통한 체액의 유동을 촉진함으로써 생체 내 체관 조직을 구조적, 기능적으로 모사한다. (b) The structure of the present invention not only prevents re-damage of phloem tubes such as lymph vessels or blood vessels during regeneration by providing appropriate physical strength and mechanical support, but also prevents re-damage of phloem tubes such as lymph vessels or blood vessels by providing appropriate physical strength and mechanical support, as well as irregularities (for example, H-beams) or lumen ( For example, by using a simple rod structure (in the form of a tube) to promote the flow of body fluid through capillary action, it structurally and functionally mimics the phloem tissue in vivo.
(c) 본 발명의 구조체는 병변부에 이식된 뒤 체관 재생 완료 후 적절한 시기에 분해됨으로써, 림프액의 유동 차단 또는 혈류의 감소로 인해 발생하는 다양한 병적 상태에 대한 효율적인 치료 수단으로 유용하게 이용될 수 있다. (c) The structure of the present invention is implanted in the lesion area and decomposed at an appropriate time after completion of phloem regeneration, so it can be usefully used as an efficient treatment method for various pathological conditions caused by blockage of lymphatic fluid flow or reduction of blood flow. there is.
도 1은 본 발명의 림프관 복원 유도 생체적합성 구조체를 적용함으로써 림프관이 정상화되는 과정을 보여주는 모식도이다.
도 2는 본 발명의 생체적합성 구조체의 정면도이다.
도 3은 본 발명의 생체적합성 구조체를 토끼 모델에 이식한 뒤 6주 경과 후 림프관 흐름 확인을 위해 ICG(indocyanine green) 형광 염색을 통하여 확인한 이미지이다.
도 4는 실험 동물에서 본 발명의 구조체가 이식된 조직을 추출하고 횡방향 (도 4a)및 종방향(도 4b)으로 절편화한 뒤, H&E(hematoxylin & eosin) 염색 및 MT (masson’s trichrome) 염색을 수행한 결과를 각각 보여준다.
도 5는 각 실험 동물 내 구조체가 이식된 부분을 대상으로 LYVE-1 및 CD31을 표적으로 한 면역형광염색을 수행한 결과를 보여주는 그림이다.Figure 1 is a schematic diagram showing the process of normalizing lymphatic vessels by applying the biocompatible structure for inducing lymphatic vessel restoration of the present invention.
Figure 2 is a front view of the biocompatible structure of the present invention.
Figure 3 is an image confirmed through ICG (indocyanine green) fluorescence staining to confirm lymphatic flow 6 weeks after transplanting the biocompatible construct of the present invention into a rabbit model.
Figure 4 shows the tissue in which the construct of the present invention was implanted in an experimental animal, extracted, sectioned in the transverse direction (Figure 4a) and longitudinal direction (Figure 4b), and then stained with H&E (hematoxylin & eosin) and MT (masson's trichrome) staining. Shows the results of performing each.
Figure 5 is a picture showing the results of immunofluorescence staining targeting LYVE-1 and CD31 on the area where the structure was implanted in each experimental animal.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예Example
제조예 1: 림프관 복원용 생체적합성 구조체의 제조Preparation Example 1: Preparation of a biocompatible structure for lymphatic vessel restoration
3차원 고분자 구조체를 제조하기 위해 3D 프린터(RAISE 3D, USA)를 사용하였으며, 3D 프린팅 기법은 노즐의 직경, 온도, 토출압력, 노즐의 이동속도 등의 조건에 따라 3차원 구조체의 사이즈를 손쉽게 조절할 수 있다. 본 발명자들은 높이 0.2 mm, 직경 0.4 mm인 스트랜드들이 도 2a에서 보는 바와 같이 각각 H 빔 및 관 형태로 적층되어 림프관과 유사한 3차원 구조를 가지는 구조체를 제작하였다. 원료 고분자로 폴리카프로락톤(PCL, Polycaprolactone, Sigma-Aldrich, USA)을 사용하였으며, 제작을 위해 노즐의 직경을 0.4 mm, 노즐 온도를 130℃, 출력 속도 6 mm/s, 노즐의 이동속도를 6 mm/s로 세팅하였다. 세팅이 완료된 상태로 H 빔과 관 형태가 각각 직경 0.8 mm, 1 mm, 높이 0.6 mm, 0.8 mm를 가지는 3차원 구조체를 제작하였다. 이후 실험에 사용하기 전에 e-beam으로 멸균처리를 수행하였다. A 3D printer (RAISE 3D, USA) was used to manufacture the 3D polymer structure, and the 3D printing technique allows the size of the 3D structure to be easily adjusted according to conditions such as nozzle diameter, temperature, discharge pressure, and nozzle movement speed. You can. The present inventors fabricated a structure with a three-dimensional structure similar to a lymphatic vessel by stacking strands with a height of 0.2 mm and a diameter of 0.4 mm in the form of an H beam and a tube, respectively, as shown in Figure 2a. Polycaprolactone (PCL, Polycaprolactone, Sigma-Aldrich, USA) was used as the raw polymer. For manufacturing, the nozzle diameter was set to 0.4 mm, the nozzle temperature was set to 130°C, the output speed was set to 6 mm/s, and the nozzle moving speed was set to 6. It was set to mm/s. With the setting complete, a three-dimensional structure with H-beam and tube shapes having diameters of 0.8 mm and 1 mm, and heights of 0.6 mm and 0.8 mm, respectively, was manufactured. Before use in subsequent experiments, sterilization was performed using an e-beam.
실험예 1: 인장강도 평가Experimental Example 1: Tensile strength evaluation
본 발명자들은 본 발명의 림프관 유사 생체적합성 구조체의 물리적 특성을 확인하기 위하여 인장강도 평가를 수행하였다. 인장강도 측정을 위해 만능시험기 (UNITEST M1, Korea)를 이용하였고, 그립간 거리 65 mm, 인장속도 50 mm/min 으로 설정하여 인장강도를 평가하였다. The present inventors performed tensile strength evaluation to confirm the physical properties of the lymphatic vessel-like biocompatible structure of the present invention. To measure the tensile strength, a universal testing machine (UNITEST M1, Korea) was used, and the tensile strength was evaluated by setting the distance between grips to 65 mm and the tensile speed to 50 mm/min.
인장강도 평가 결과 H 빔 생체적합성 구조체의 인장강도는 15.39 MPa, 관형태 생체적합성 구조체 인장강도는 15.92 MPa로 관형태의 생체적합성 구조체가 좀더 높은 인장강도를 가지고 있으며, H 빔 생체적합성 구조체의 탄성계수는 4.90 MPa, 관형태 생체적합성 구조체 인장강도는 4.19 MPa로 H 빔 생체적합성 구조체의 강성도가 더 높은 것을 알 수 있다. As a result of the tensile strength evaluation, the tensile strength of the H-beam biocompatible structure was 15.39 MPa, and the tensile strength of the tubular biocompatible structure was 15.92 MPa. The tubular biocompatible structure had a higher tensile strength, and the elastic modulus of the H-beam biocompatible structure was 15.92 MPa. is 4.90 MPa, and the tensile strength of the tubular biocompatible structure is 4.19 MPa, showing that the stiffness of the H-beam biocompatible structure is higher.
실험예 2: 토끼 모델 동물실험Experimental Example 2: Rabbit model animal experiment
본 발명자들은 본 발명의 림프관 유사 생체적합성 구조체의 이식으로 의해 림프관 재생이 유도되는지 여부를 평가하고자 하였다. 뉴질랜드 화이트 토끼(10주령, 암컷)의 오금에 위치한 림프관을 2cm 절제 후 남은 림프관을 림프절에 봉합한 그룹, 본 발명의 H 빔 형태 구조체를 림프절 및 림프관에 봉합한 그룹, 본 발명의 관 형태 구조체를 림프절 및 림프관에 봉합한 그룹, 그리고 정상 림프관 그룹의 총 4개의 그룹으로 나누어 실험을 진행하였다.The present inventors sought to evaluate whether lymphatic vessel regeneration is induced by transplantation of the lymphatic vessel-like biocompatible construct of the present invention. A group in which a lymphatic vessel located in the popliteal fossa of a New Zealand white rabbit (10 weeks old, female) was excised by 2 cm and the remaining lymphatic vessels were sutured to the lymph nodes, a group in which the H-beam-shaped structure of the present invention was sutured to the lymph nodes and lymphatic vessels, and a group in which the tube-shaped structure of the present invention was sutured to the lymph nodes and lymphatic vessels. The experiment was conducted by dividing the subjects into four groups: a group with sutured lymph nodes and lymphatic vessels, and a group with normal lymphatic vessels.
봉합 후 6주가 경과한 시점에서 10% ICG(indocyanine green) 형광물질을 발 지간 부위에 1cc 가량 피하 주사하고 절제술을 진행한 림프관 및 림프절을 조영하여 흐름을 검사하고(도 3a 및 3b), 각 실험 동물을 희생시켜 구조체가 이식된 부분의 조직을 추출하여 횡방향 및 종방향으로 절편화한 뒤, H&E(hematoxylin & eosin) 염색 및 MN(masson’s trichrome) 염색(도 4a 및 4b) 그리고 LYVE-1(lymphatic vessel endothelial hyaluronic acid receptor 1), CD31 (cluster of differentiation 31) 항원을 대상으로 면역형광염색(Immunofluoresence)을 수행하였다(도 5). Six weeks after suturing, approximately 1 cc of 10% ICG (indocyanine green) fluorescent material was subcutaneously injected into the interphalangeal area of the foot, and the lymphatic vessels and lymph nodes where the resection was performed were contrasted to examine the flow (Figures 3a and 3b), and each experiment The animal was sacrificed, the tissue from the area where the construct was implanted was extracted, sectioned transversely and longitudinally, H&E (hematoxylin & eosin) staining, MN (masson's trichrome) staining (Figures 4a and 4b), and LYVE-1 ( Immunofluorescence staining was performed on lymphatic vessel endothelial hyaluronic acid receptor 1) and CD31 (cluster of differentiation 31) antigens (Figure 5).
림프관 흐름 검사에 사용되는 ICG가 주사 부위인 발에서 절제술 진행한 오금 림프관까지 잘 조영되었음을 관찰하여, 형광 시약이 각 구조체를 통하여 잘 순환한 것을 확인하였다. 이를 통해 본 발명의 H 빔 구조체와 관 형태 구조체 모두 대체 림프관으로써의 기능을 수행할 수 있음을 확인하였다. It was observed that the ICG used in the lymphatic flow test contrasted well from the injection site, the foot, to the popliteal lymphatic vessel where the resection was performed, confirming that the fluorescent reagent circulated well through each structure. Through this, it was confirmed that both the H-beam structure and the tubular structure of the present invention can perform the function as an alternative lymphatic vessel.
그리고 H&E와 MT 염색을 통하여 H 빔 형태 구조체가 이식된 경우 H 빔 구조체 주위로 근육이, 관 형태 구조체의 경우 구조체 주위로 콜라겐이 차오른 것을 관찰하였다. 림프관의 경우 림프액이 흐르는 내부 공간과 맞닿는 부위는 림프 내피 세포로 이뤄져 있고, 이런 내피 세포를 평활근이 감싸는 형태이며 림프모세관은 림프 내피 세포를 콜라겐 섬유가 감싸는 형태로 이뤄져 있다. 이러한 양상은 본 발명의 H 빔 형태 구조체는 림프관 형태를, 본 발명의 관 형태 구조체는 림프모세관의 형태를 각각 모사함으로써 림프관과 림프모세관으로의 재생을 효율적으로 유도함을 확인할 수 있었다. Additionally, through H&E and MT staining, it was observed that muscle had built up around the H-beam structure when the H-beam structure was implanted, and collagen had built up around the structure in the case of a tubular structure. In the case of lymphatic vessels, the area in contact with the internal space through which lymph fluid flows is made up of lymphatic endothelial cells, and smooth muscles surround these endothelial cells, and lymphatic capillaries are made up of collagen fibers surrounding lymphatic endothelial cells. This aspect confirmed that the H-beam-shaped structure of the present invention mimics the shape of a lymphatic vessel and the tube-shaped structure of the present invention mimics the shape of a lymphatic capillary, thereby efficiently inducing regeneration into lymphatic vessels and lymphatic capillaries.
림프관 형성 및 재생은 림프 내피세포에 의해서 시작되므로 림프 내피 세포는 림프관 재생의 중요한 지표이다. LYVE-1은 림프 내피 세포에 존재하는 수용체로 LYVE-1 염색을 통해 림프 내피 세포의 존재를 확인할 수 있다. 또한 CD31은 주로 혈소판, 백혈구, 그리고 내피 세포에 존재하는 부착분자로 내피 세포가 부착하여 생장하도록 도움을 주기에 혈관 형성 및 재생의 중요한 지표이다. LYVE-1 및 CD31을 표적으로 면역형광염색을 수행한 결과, H 빔 및 관 형태 구조체 모두 림프 내피 세포가 이식한 구조체 주위로 유의하게 형성되었음을 확인하였으며, 혈관 형성에 관여하는 CD31도 관찰되었다(도 5). 이를 통해 본 발명의 H 빔 형태 구조 및 관 형태 구조에서 모두 림프관 재생이 효율적으로 유도됨을 확인할 수 있었다.Since lymphatic vessel formation and regeneration is initiated by lymphatic endothelial cells, lymphatic endothelial cells are important indicators of lymphatic vessel regeneration. LYVE-1 is a receptor present in lymphatic endothelial cells, and the presence of lymphatic endothelial cells can be confirmed through LYVE-1 staining. In addition, CD31 is an adhesion molecule mainly present in platelets, white blood cells, and endothelial cells, and is an important indicator of blood vessel formation and regeneration because it helps endothelial cells adhere and grow. As a result of immunofluorescence staining targeting LYVE-1 and CD31, it was confirmed that lymphatic endothelial cells were significantly formed around the transplanted structure for both H-beam and tubular structures, and CD31, which is involved in blood vessel formation, was also observed (Figure 5). Through this, it was confirmed that lymphatic vessel regeneration was efficiently induced in both the H-beam-shaped structure and the tube-shaped structure of the present invention.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당 업계 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현 예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred implementation examples and do not limit the scope of the present invention. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (11)
A body vessel comprising a rod-shaped biodegradable structure, wherein a cross-section of the structure includes one or more irregularities, cavities, or a combination thereof that provide a fluid pathway for body fluid. Human implants for inducing regeneration.
The human implant according to claim 1, wherein the cross section including the irregularities is an H-beam.
The human implant according to claim 1, wherein the cross-section including the irregularities is radial.
The human implant according to claim 1, wherein the lumen is circular or polygonal.
The human implant according to claim 1, wherein the cross-section has a major axis of 0.1 - 3.0 mm and a minor axis of 0.1 - 3.0 mm.
The human implant according to claim 1, wherein the lumen has an area of 0.0025 - 6.25 mm 2 .
The method of claim 1, wherein the biodegradable structure is PCL[poly(caprolactone)], PLA[poly(lactide)], PGA[poly(glycolide)], PDO[poly(dioxanone)]), and PBL[poly(butyrolactone)]. , a human implant comprising at least one biodegradable polymer selected from the group consisting of PVL [poly(valerolactone)] and PLGA [poly(lactide-co-glycolide)].
The human implant according to claim 1, wherein the body fluid is lymph fluid and the sieve tube is a lymphatic vessel.
The human implant according to claim 1, wherein the body fluid is blood and the sieve tube is a blood vessel.
A composition for treating lymphedema comprising the human implant of claim 8 as an active ingredient.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20220149370 | 2022-11-10 | ||
| KR1020220149370 | 2022-11-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20240069643A true KR20240069643A (en) | 2024-05-20 |
Family
ID=91033282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020230154228A KR20240069643A (en) | 2022-11-10 | 2023-11-09 | 3-Dimensional Biocompatible Structure for Regeneration of Body Vessel |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR20240069643A (en) |
| WO (1) | WO2024101906A1 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101683336B1 (en) * | 2014-03-10 | 2016-12-06 | 단국대학교 천안캠퍼스 산학협력단 | Biodegradable nerve conduit having channels of microstructure and manufacturing method of the same |
| US10736987B2 (en) * | 2014-12-23 | 2020-08-11 | Klinikum Rechts Der Isar Der Technischen Universität München | Implant for lymph node formation/regeneration |
| KR102002206B1 (en) * | 2016-11-09 | 2019-10-02 | 단국대학교 천안캠퍼스 산학협력단 | Stem cell culture, differentiation and transplantable biodegradable microporous micropatterned nerve guidance conduit for nerve regeneration, and biodegradable microporous micropatterned nerve guidance conduit manufactured thereby |
| KR102567367B1 (en) * | 2021-02-24 | 2023-08-17 | 성균관대학교산학협력단 | The manufacturing and implementation of microchanneled scaffold |
-
2023
- 2023-11-09 KR KR1020230154228A patent/KR20240069643A/en unknown
- 2023-11-09 WO PCT/KR2023/017938 patent/WO2024101906A1/en unknown
Non-Patent Citations (1)
| Title |
|---|
| 비특허문헌 1. Danielle H Rochlin et al., The role of adjunct nanofibrillar collagen scaffold implantation in the surgical management of secondary lymphedema: Review of the literature and summary of initial pilot studies J Surg Oncol. 121: 121-128 (2020). |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024101906A1 (en) | 2024-05-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101719081B1 (en) | Bioerodible wraps and uses therefor | |
| EP2921136B1 (en) | Fiber membranes for repairing tissue and products and preparation method thereof | |
| US20080031923A1 (en) | Biologic Replacement for Fibrin Clot | |
| US11638640B2 (en) | In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material | |
| US20150209473A1 (en) | Methods of modifying myocardial infarction expansion | |
| KR20180126436A (en) | Cell-bound composite materials for tissue reconstruction | |
| US9017709B2 (en) | Composition comprising polymeric, water-insoluble, anionic particles, processes and uses | |
| CN112384258A (en) | Nanofiber-hydrogel composites for cell and tissue delivery | |
| Jankau et al. | Bacterial cellulose properties fulfilling requirements for a biomaterial of choice in reconstructive surgery and wound healing | |
| KR20000005068A (en) | Promotion of regeneration of organized tissues | |
| EP4125715A1 (en) | In vivo tissue engineering devices, methods and regenerative and cellular medicine employing scaffolds made of absorbable material | |
| EP3934707B1 (en) | Biodegradable mesh implant for soft tissue repair, in particular hernia repair | |
| CN115845141A (en) | Preparation method and application of dry amnion | |
| Zhao et al. | Duraplasty of PHBV/PLA/Col membranes promotes axonal regeneration by inhibiting NLRP3 complex and M1 macrophage polarization in rats with spinal cord injury | |
| Lee et al. | Breast reconstruction | |
| KR20240069643A (en) | 3-Dimensional Biocompatible Structure for Regeneration of Body Vessel | |
| Nazari et al. | Advancing standard techniques for treatment of perianal fistula; when tissue engineering meets seton | |
| de Souza et al. | 3D printed wound constructs for skin tissue engineering: A systematic review in experimental animal models | |
| CN102671243A (en) | Quaternized chitosan/siRNA composite particle-loaded skin regeneration material and preparation method thereof | |
| KR102671293B1 (en) | Adhesive matrix for bioadhesion | |
| Safi et al. | Nanoskin?—The Impact of Natural Membrane on COVID-19 and Chronic Wound | |
| KR20230103926A (en) | 3-Dimensional Biocompatible Structure for Tissue Repair | |
| AU2022328865A1 (en) | Fucan and modified fucan compositions for the treatment of conditions related to capsular contracture and to inhibiting fibrous growth around or on transplants | |
| Murphy et al. | Peripheral nervous system responses to biomaterials | |
| AU2008309625B2 (en) | Device for administering cells and cell-therapy methods using said device |