EP2566426A1 - Kit for obtaining and processing a material derived from a physiological tissue - Google Patents
Kit for obtaining and processing a material derived from a physiological tissueInfo
- Publication number
- EP2566426A1 EP2566426A1 EP10736804A EP10736804A EP2566426A1 EP 2566426 A1 EP2566426 A1 EP 2566426A1 EP 10736804 A EP10736804 A EP 10736804A EP 10736804 A EP10736804 A EP 10736804A EP 2566426 A1 EP2566426 A1 EP 2566426A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- rotor
- kit according
- clot
- kit
- membrane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000463 material Substances 0.000 title claims abstract description 14
- 238000012545 processing Methods 0.000 title claims abstract description 11
- 210000004369 blood Anatomy 0.000 claims abstract description 10
- 239000008280 blood Substances 0.000 claims abstract description 10
- 239000012528 membrane Substances 0.000 claims abstract description 7
- 230000003750 conditioning effect Effects 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 210000001519 tissue Anatomy 0.000 claims description 23
- 108010073385 Fibrin Proteins 0.000 claims description 12
- 102000009123 Fibrin Human genes 0.000 claims description 12
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 12
- 229950003499 fibrin Drugs 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 5
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 239000000560 biocompatible material Substances 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 239000003102 growth factor Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 230000029663 wound healing Effects 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 4
- 210000004623 platelet-rich plasma Anatomy 0.000 description 4
- 239000003634 thrombocyte concentrate Substances 0.000 description 4
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 102000008108 Osteoprotegerin Human genes 0.000 description 2
- 108010035042 Osteoprotegerin Proteins 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 239000000282 fibrinogen degradation product Substances 0.000 description 2
- 230000002070 germicidal effect Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 102000006877 Pituitary Hormones Human genes 0.000 description 1
- 108010047386 Pituitary Hormones Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 230000010478 bone regeneration Effects 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000000960 hypophysis hormone Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000004261 periodontium Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/10—Apparatus for enzymology or microbiology rotatably mounted
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3616—Blood, e.g. platelet-rich plasma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/02—Adhesive bandages or dressings
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
- C12M1/12—Apparatus for enzymology or microbiology with sterilisation, filtration or dialysis means
- C12M1/121—Apparatus for enzymology or microbiology with sterilisation, filtration or dialysis means with sterilisation means
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M45/00—Means for pre-treatment of biological substances
- C12M45/05—Means for pre-treatment of biological substances by centrifugation
Definitions
- the present invention relates to the recovering, treatment and processing of physiological tissues, and particularly it relates to a kit for the recovering and processing of physiological tissues as well as to a method of recovering, treatment and processing of physiological tissues.
- Fibrin Glue (Tissucol Baxter), Platelet Concentrate cPRP (Marx 1998), Platelet-Rich Plasma (PRP), Plasma-Rich Growth Factors (PRGFs, E.Anitua), Fibrin-Rich Plasma (2001 J.Choukroun).
- a method of obtaining a material based on the use of growth factors has been designed.
- Growth factors can be naturally occurring, and therefore they can be extracted from tissues or cells and processed: Pituitary Hormones, Platelet Derived Growth Factors (PDGFs), Calcitonin, Insulin-Like Growth Factors (IGFs), Fibroblast Growth Factors (FGFs), cytokines, especially IL-1 and TNF-a, osteoprotegerin (OPG), insulin-like GFs (IGF-I and IGF-II), etc.; otherwise they can be synthetic, and therefore they can be completely synthesized: GF, ALP, BMP, etc.
- the search according to the present invention led to the isolation of a material derived from physiological tissues which can be used directly to reconstruct tissues and which is easy to be tained. Such a material will be hereinafter referred to with the acronym C.G.F. (concentrated growth factor).
- C.G.F. is a wound-healing biomaterial having absolutely special features and characteristics with respect to comparable platelet concentrates.
- the process of preparation thereof, its biochemical aspects, its structure, the composition of the clot, the structure of fibrin, the role of platelet cytokines, the leukocyte activation, the potential interaction between C.G.F. and bone cells, its potential use with soft tissues and bone regeneration all make it a biomaterial easy to be produced and used in several clinical applications with very surprising results.
- C.G.F induces both an improved wound-healing of tissues due to the development of an effective neo-vascularization, and a surgical wound healing associated to a fast remodelling of scar tissues with almost no infectious sequelae.
- PRP the technique of extraction thereof doesn't require any other components added besides of blood (in the case of PRP, thrombin and calcium chloride are added).
- periodontology is useful in stabilizing the marginal periodontium as well as in obtaining optimal aesthetic results for the restorations. It allows the initial bone volume to be maintained or reconstructed by promoting the alignment of tooth necks and the presence of papillae, resulting in an improved profile of emergence for the prosthetic restorations.
- C.G.F. facilitates the operatory management of surgical sites and enhances the incorporation and remodelling of grafted biomaterials.
- C.G.F. consists of an autologous fibrin matrix inherently having a high amount of plasma cytokines and leukocyte-derived cytokines incorporated therein; it can be said that this immune platelet concentrate is characterized by f ou r key-featu res : ibrin clot plays a very important mechanical role due to its stiffness, and when its particles are mixed with graft material, they form a biological cross- linker.
- the immune aspect is very important due to the existence of leucocytes in the clot to incorporate inflammatory and anti-inflammatory cytokines.
- the progressive regulation of these molecules appears to play a self-regulating role for inflammatory and infectious phenomena at the graft site.
- fibrin alone can induce angiogenesis. This extremely important property can be explained by both the three-dimensional structure of fibrin gel and the combined action of cytokines trapped in its meshes.
- Fibrin- and fibrinogen-degradation products stimulate the migration of neutrophils and increase the ability of the CD11/CD18 receptors on the surface thereof, which receptors allow the neutrophils not only to adhere to the endothelium and transmigrate, but also to adhere to fibrinogen at the same time. Furthermore, these components modulate phagocytosis and enzymatic degradation processes.
- the fibrin matrix carries out the coverage healing of the damaged sites by acting on epithelial cells and fibroblasts. All these elements of meditation allow us to identify C.G.F. as a fibrin clot able to develop a micro- vascularization while having the ability of driving the migration of epithelial cells to its surface.
- the object of the present invention is a kit for obtaining and processing a material derived from a physiological tissue and particularly from human blood, comprising separating means for removing a fraction of the physiological tissue; mixing means for conditioning said previously removed fraction; injecting means for injecting the clot, membrane-forming means for producing a membrane from the clot, and positioning means for positioning the resulting membrane.
- Said separating means includes a centrifuge properly designed to separate the fibrin and clot from the blood, which centrifuge can operate at a given speed and with a suitable configuration of the rotor; furthermore, said centrifuge is provided with means for sterilizing the processed tissues.
- said sterilizing means includes an ultraviolet ray lamp.
- the mixing means for conditioning the removed fraction includes a rotary mixer which allows the physiological tissue to be mixed with optional charges which can include other biological tissues such as bone tissues, or other biocompatible materials.
- Figure 1 A is an elevation view with parts broken-away and sectioned of a first component of the kit according to the present invention
- Figure 1 B is a side elevation view of the component of Figure 1A;
- Figure 2 is a plan view with sectioned parts of a second component of the kit according to the present invention.
- Figure 3 is a plan view of a third component of the kit according to the present invention.
- Figure 4 is a broken-away and enlarged detail of Figure 3;
- Figure 5 is the same detail as of Figure 4 in a side elevation; and Figures 6 and 7 are both views of a fourth component of the kit according to the present invention.
- FIG 1A there is shown a first component of the kit according to the present invention
- reference numeral 1 designates the body of the centrifuge provided with a lid 101 enclosing the chamber 201 in which the rotor 301 is located, the rotor being provided with housings 311 intended for accommodating the test tubes 401.
- the centrifuge 1 internally has a germicidal lamp 501 facing toward the chamber 201.
- the centrifuge which is designed to process freshly withdrawn blood, has certain features: firstly, a one-piece rotor 301 with a properly sized tilt angle of the test tube, particularly with a tilt angle within the range of 30° to 50° with respect to the revolution axis of the rotor.
- a UV germicidal lamp 501 is fitted within the chamber 201 to optimize the security of processing operations in terms of sepsis.
- Acceleration and braking are controlled to avoid troubles while separating the material being subjected to the action of the centrifuge. Cooling of the rotor is also controlled to achieve an increased level of performance. Test tube-holders can be conveniently sterilized using an autoclave. Finally, the centrifuge provides for the automatic opening of the lid when a cycle has finished.
- FIG. 2 there is shown a second component of the kit according to the present invention; reference numeral 2 designates the fibrin injector.
- Such an injector includes a first cylinder 102 to which a piston is slidably fitted, the piston sliding within the chamber 112 formed in the cylinder 102.
- the cylinder 102 is provided with grasping means in the form of rings 142, and similarly, the ring 222 provides grasping means for the piston 202.
- a flexible stem 212 is fitted within the piston, and it is extended through the restriction 122 of the chamber 112 and the conduit 302 fitted within the axial cavity 132 in communication with said restriction 122.
- the other end of the conduit is fitted to the end of the second cylinder 402 at 412, and the piston 2 driven by the flexible stem 212 connected thereto slides within the chamber 422 of the second cylinder 402.
- the end 442 of the second cylinder 402 is fitted to the axial cavity 612 in communication with the chamber 642 of the third cylinder 602.
- the piston 622 provided with sealing means 632 slides within the third cylinder 602.
- the cylinder has a radial flange 652 protruding outwardly as a handle.
- FIG. 3 there is shown a third component of the kit according to the present invention
- reference numeral 3 designates the membrane-forming tool which produces a membrane by processing the biological tissue according to the present invention.
- the membrane-forming tool 3 is a nipper with two arms 103 provided with grasping rings 113 at one end thereof, which arms are pivoted at 203 and provided at the opposite end with extensions 303 to which two disks 403 are respectively attached.
- Figure 4 there is shown a detail of Figure 3 with sectioned parts; like reference numerals refer to like parts.
- Figure 5 further elucidates the location of the extension 303, plate 313 and attaching means 323.
- FIGs 6 and 7 there is shown a fourth component of the kit according to the present invention
- reference numeral 4 designates the applicator tool, comprising a stylus 104 to whose ends there are connected two bushes 114 carrying a paddle-like member 124 respectively; as it can be noted from Figure 7, both the paddles 124 are oriented at 180° to each other. The curvature shape of each paddle is also characteristic.
- the operation of the kit according to the present invention will become apparent from the following.
- the whole blood tissue is taken from the same patient to whom the scar reconstruction has to be applied.
- Blood is treated with the centrifuge as designed for the kit according to the invention, and ee phases are separated: plasma, fibrin component and red-cell component with platelets.
- the fibrin concentrate is then mixed with the blot and optional charges in the rotary mixer, and it can be subsequently subjected to further processing steps.
- the resulting tissue is characterized by the formation of an elastic multi-molecular web with a high potential of configuration; therefore, it is possible to produce membranous structures which can be easily applied to the area intended to be treated.
- the obtained material could be injected by extrusion by means of the injector; the material is introduced in the third cylinder of the injector, that is to say the one having the greater section, and then it is charged in the portion of the device which is able to feed it in the cavity that has to be subjected to the treatment.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Botany (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Sustainable Development (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Materials Engineering (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Materials For Medical Uses (AREA)
- External Artificial Organs (AREA)
Abstract
Kit for obtaining and processing a material derived from a physiological tissue and particularly from human blood, comprising separating means for removing a fraction of the physiological tissue; mixing means for conditioning said previously removed fraction; injecting means for injecting the clot, membrane-forming means for producing a membrane from the clot, and positioning means for positioning the resulting membrane.
Description
KIT FOR OBTAINING AND PROCESSING A MATERIAL
DERIVED FROM A PHYSIOLOGICAL TISSUE
TEXT OF THE DESCRIPTION The present invention relates to the recovering, treatment and processing of physiological tissues, and particularly it relates to a kit for the recovering and processing of physiological tissues as well as to a method of recovering, treatment and processing of physiological tissues.
The search for protocols promoting both haemostasis and wound healing is an issue encountered in all the surgical fields. The dream for all the surgeons is to have a miraculous glue which can both repair wounds without causing necrosis and simultaneously prevent all the sequelae of each surgical operation (infections, hematomas, tearing, etc.). Typically, blood is the most available tissue which can be easily obtained substantially from every type of patient. Various types of tissues are known which can be useful in producing surgically processable materials. Among these: Fibrin Glue (Tissucol Baxter), Platelet Concentrate cPRP (Marx 1998), Platelet-Rich Plasma (PRP), Plasma-Rich Growth Factors (PRGFs, E.Anitua), Fibrin-Rich Plasma (2001 J.Choukroun).
According to the present invention, a method of obtaining a material based on the use of growth factors has been designed.
Growth factors can be naturally occurring, and therefore they can be extracted from tissues or cells and processed: Pituitary Hormones, Platelet Derived Growth Factors (PDGFs), Calcitonin, Insulin-Like Growth Factors (IGFs), Fibroblast Growth Factors (FGFs), cytokines, especially IL-1 and TNF-a, osteoprotegerin (OPG), insulin-like GFs (IGF-I and IGF-II), etc.; otherwise they can be synthetic, and therefore they can be completely synthesized: GF, ALP, BMP, etc. The search according to the present invention led to the isolation of a material derived from physiological tissues which can be used directly to reconstruct tissues and which is easy to be
tained. Such a material will be hereinafter referred to with the acronym C.G.F. (concentrated growth factor).
C.G.F. is a wound-healing biomaterial having absolutely special features and characteristics with respect to comparable platelet concentrates. The process of preparation thereof, its biochemical aspects, its structure, the composition of the clot, the structure of fibrin, the role of platelet cytokines, the leukocyte activation, the potential interaction between C.G.F. and bone cells, its potential use with soft tissues and bone regeneration all make it a biomaterial easy to be produced and used in several clinical applications with very surprising results.
C.G.F induces both an improved wound-healing of tissues due to the development of an effective neo-vascularization, and a surgical wound healing associated to a fast remodelling of scar tissues with almost no infectious sequelae.
In contrast with all the other platelet concentrates, and particularly
PRP, the technique of extraction thereof doesn't require any other components added besides of blood (in the case of PRP, thrombin and calcium chloride are added).
Its utilization in periodontology is useful in stabilizing the marginal periodontium as well as in obtaining optimal aesthetic results for the restorations. It allows the initial bone volume to be maintained or reconstructed by promoting the alignment of tooth necks and the presence of papillae, resulting in an improved profile of emergence for the prosthetic restorations.
Use of C.G.F. facilitates the operatory management of surgical sites and enhances the incorporation and remodelling of grafted biomaterials. C.G.F. consists of an autologous fibrin matrix inherently having a high amount of plasma cytokines and leukocyte-derived cytokines incorporated therein; it can be said that this immune platelet concentrate is characterized by f ou r key-featu res :
ibrin clot plays a very important mechanical role due to its stiffness, and when its particles are mixed with graft material, they form a biological cross- linker.
- when fragments of graft material are supplemented with particles of C.G.F., cell migration and particularly endothelial cell migration is promoted, resulting in a neo-angiogenesis which is critical for the vascularization and survival of the graft;
- plasma cytokines allow to obtain a steady wound healing phenomenon based on the reabsorption of the fibrin matrix;
- finally, the immune aspect is very important due to the existence of leucocytes in the clot to incorporate inflammatory and anti-inflammatory cytokines. The progressive regulation of these molecules appears to play a self-regulating role for inflammatory and infectious phenomena at the graft site.
It has been shown that fibrin alone can induce angiogenesis. This extremely important property can be explained by both the three-dimensional structure of fibrin gel and the combined action of cytokines trapped in its meshes.
Fibrin- and fibrinogen-degradation products stimulate the migration of neutrophils and increase the ability of the CD11/CD18 receptors on the surface thereof, which receptors allow the neutrophils not only to adhere to the endothelium and transmigrate, but also to adhere to fibrinogen at the same time. Furthermore, these components modulate phagocytosis and enzymatic degradation processes.
The fibrin matrix carries out the coverage healing of the damaged sites by acting on epithelial cells and fibroblasts. All these elements of meditation allow us to identify C.G.F. as a fibrin clot able to develop a micro- vascularization while having the ability of driving the migration of epithelial cells to its surface.
The object of the present invention is a kit for obtaining and processing a material derived from a physiological tissue and particularly from human blood, comprising separating means for removing a fraction of the physiological tissue; mixing means for conditioning said previously removed fraction; injecting means for injecting the clot, membrane-forming means for producing a membrane from the clot, and positioning means for positioning the resulting membrane.
Said separating means includes a centrifuge properly designed to separate the fibrin and clot from the blood, which centrifuge can operate at a given speed and with a suitable configuration of the rotor; furthermore, said centrifuge is provided with means for sterilizing the processed tissues. Preferably, said sterilizing means includes an ultraviolet ray lamp.
The mixing means for conditioning the removed fraction includes a rotary mixer which allows the physiological tissue to be mixed with optional charges which can include other biological tissues such as bone tissues, or other biocompatible materials.
Other advantages and features of the present invention will be apparent from the following description of an embodiment thereof, which is provided by way of illustration, and not by way of limitation, with reference to the accompanying drawings wherein:
Figure 1 A is an elevation view with parts broken-away and sectioned of a first component of the kit according to the present invention;
Figure 1 B is a side elevation view of the component of Figure 1A;
Figure 2 is a plan view with sectioned parts of a second component of the kit according to the present invention;
Figure 3 is a plan view of a third component of the kit according to the present invention;
Figure 4 is a broken-away and enlarged detail of Figure 3;
Figure 5 is the same detail as of Figure 4 in a side elevation; and
Figures 6 and 7 are both views of a fourth component of the kit according to the present invention.
In Figure 1A there is shown a first component of the kit according to the present invention; reference numeral 1 designates the body of the centrifuge provided with a lid 101 enclosing the chamber 201 in which the rotor 301 is located, the rotor being provided with housings 311 intended for accommodating the test tubes 401. In Figure 1 B, the centrifuge 1 internally has a germicidal lamp 501 facing toward the chamber 201. The centrifuge, which is designed to process freshly withdrawn blood, has certain features: firstly, a one-piece rotor 301 with a properly sized tilt angle of the test tube, particularly with a tilt angle within the range of 30° to 50° with respect to the revolution axis of the rotor. A UV germicidal lamp 501 is fitted within the chamber 201 to optimize the security of processing operations in terms of sepsis.
Acceleration and braking are controlled to avoid troubles while separating the material being subjected to the action of the centrifuge. Cooling of the rotor is also controlled to achieve an increased level of performance. Test tube-holders can be conveniently sterilized using an autoclave. Finally, the centrifuge provides for the automatic opening of the lid when a cycle has finished.
In Figure 2 there is shown a second component of the kit according to the present invention; reference numeral 2 designates the fibrin injector. Such an injector includes a first cylinder 102 to which a piston is slidably fitted, the piston sliding within the chamber 112 formed in the cylinder 102. The cylinder 102 is provided with grasping means in the form of rings 142, and similarly, the ring 222 provides grasping means for the piston 202. A flexible stem 212 is fitted within the piston, and it is extended through the restriction 122 of the chamber 112 and the conduit 302 fitted within the axial cavity 132 in communication with said restriction 122. The other end of the conduit is fitted to the end of the second cylinder 402 at 412, and the piston
2 driven by the flexible stem 212 connected thereto slides within the chamber 422 of the second cylinder 402.
The end 442 of the second cylinder 402 is fitted to the axial cavity 612 in communication with the chamber 642 of the third cylinder 602. The piston 622 provided with sealing means 632 slides within the third cylinder 602. The cylinder has a radial flange 652 protruding outwardly as a handle.
In Figure 3 there is shown a third component of the kit according to the present invention; reference numeral 3 designates the membrane-forming tool which produces a membrane by processing the biological tissue according to the present invention. The membrane-forming tool 3 is a nipper with two arms 103 provided with grasping rings 113 at one end thereof, which arms are pivoted at 203 and provided at the opposite end with extensions 303 to which two disks 403 are respectively attached.
In Figure 4 there is shown a detail of Figure 3 with sectioned parts; like reference numerals refer to like parts. In the figure there is shown how the respective disk 403 is secured to the extension 303 through the drilled plate 313 in which there is fitted the screw 323 which is screwed in the threaded hole 423 formed at the centre of the axial tang 413 protruding from the disk 403. Figure 5 further elucidates the location of the extension 303, plate 313 and attaching means 323.
In Figures 6 and 7 there is shown a fourth component of the kit according to the present invention; reference numeral 4 designates the applicator tool, comprising a stylus 104 to whose ends there are connected two bushes 114 carrying a paddle-like member 124 respectively; as it can be noted from Figure 7, both the paddles 124 are oriented at 180° to each other. The curvature shape of each paddle is also characteristic.
The operation of the kit according to the present invention will become apparent from the following. The whole blood tissue is taken from the same patient to whom the scar reconstruction has to be applied. Blood is treated with the centrifuge as designed for the kit according to the invention, and
ee phases are separated: plasma, fibrin component and red-cell component with platelets. The fibrin concentrate is then mixed with the blot and optional charges in the rotary mixer, and it can be subsequently subjected to further processing steps. The resulting tissue is characterized by the formation of an elastic multi-molecular web with a high potential of configuration; therefore, it is possible to produce membranous structures which can be easily applied to the area intended to be treated.
Similarly, the obtained material could be injected by extrusion by means of the injector; the material is introduced in the third cylinder of the injector, that is to say the one having the greater section, and then it is charged in the portion of the device which is able to feed it in the cavity that has to be subjected to the treatment.
Claims
1. Kit for obtaining and processing a material derived from a physiological tissue and particularly from human blood, comprising separating means for removing a fraction of the physiological tissue; mixing means for conditioning said previously removed fraction; injecting means for injecting the clot, membrane-forming means for producing a membrane from the clot, and positioning means for positioning the resulting membrane.
2. Kit according to claim 1 , wherein said separating means includes a centrifuge properly designed to separate the fibrin and clot from the blood, which centrifuge can operate at a given speed and with a suitable configuration of the rotor, positioned in a suitable chamber.
3. Kit according to claim 2, wherein the test tube-holders of said rotor are tilted by an angle within the range of 30° to 50° with respect to the revolution axis of the rotor.
4. Kit according to claim 3, wherein the test tube-holders of said rotor are tilted by an angle of 32°.
5. Kit according to anyone of the preceding claims 1 to 4, wherein said centrifuge is provided with means for sterilizing the chamber in which the said rotor is positioned.
6. Kit according to claim 5, wherein said sterilizing means includes an ultraviolet ray lamp.
7. Device according to any one of the preceding claims 1 to 6, wherein said mixing means for conditioning the removed fraction includes a rotary mixer which allows the physiological tissue to be mixed with optional charges which can include other biological tissues such as bone tissues, or other biocompatible materials.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IT2010/000200 WO2011138803A1 (en) | 2010-05-06 | 2010-05-06 | Kit for obtaining and processing a material derived from a physiological tissue |
Publications (1)
Publication Number | Publication Date |
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EP2566426A1 true EP2566426A1 (en) | 2013-03-13 |
Family
ID=44140797
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP10736804A Withdrawn EP2566426A1 (en) | 2010-05-06 | 2010-05-06 | Kit for obtaining and processing a material derived from a physiological tissue |
Country Status (4)
Country | Link |
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EP (1) | EP2566426A1 (en) |
KR (1) | KR20130107197A (en) |
CN (1) | CN102869328A (en) |
WO (1) | WO2011138803A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN106890732A (en) * | 2017-04-07 | 2017-06-27 | 长沙湘智离心机仪器有限公司 | A kind of beauty centrifuge and its operating method |
US11191698B2 (en) * | 2017-11-03 | 2021-12-07 | Enso Discoveries, Llc | Apparatus and method for processing platelet rich fibrin |
EP3650531A1 (en) * | 2018-11-09 | 2020-05-13 | DSM IP Assets B.V. | Adipose tissue processing device |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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IT1230059B (en) * | 1989-04-17 | 1991-09-27 | Dorin Olimpiu Petrescu | PROCEDURE FOR IN VITRO PREPARATION OF ARTIFICIAL HEMOSTATIC MEMBRANES. |
US7608258B2 (en) * | 2002-04-13 | 2009-10-27 | Allan Mishra | Method for treatment of tendinosis using platelet rich plasma |
ITMI20022501A1 (en) * | 2002-11-26 | 2004-05-27 | Dorin Olimpiu Petrescu | ORGANIC CICATRIZING AND HEMOSTATIC DRESSING. |
EP1906737A4 (en) * | 2005-06-30 | 2010-07-07 | Cytomedix Inc | Method for treating wounds with enriched platelet wound healant |
-
2010
- 2010-05-06 KR KR1020127030633A patent/KR20130107197A/en not_active Application Discontinuation
- 2010-05-06 EP EP10736804A patent/EP2566426A1/en not_active Withdrawn
- 2010-05-06 CN CN2010800666008A patent/CN102869328A/en active Pending
- 2010-05-06 WO PCT/IT2010/000200 patent/WO2011138803A1/en active Application Filing
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Also Published As
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WO2011138803A1 (en) | 2011-11-10 |
KR20130107197A (en) | 2013-10-01 |
CN102869328A (en) | 2013-01-09 |
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