WO1994018906A1 - Organe artificiel implantable - Google Patents

Organe artificiel implantable Download PDF

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Publication number
WO1994018906A1
WO1994018906A1 PCT/US1994/001734 US9401734W WO9418906A1 WO 1994018906 A1 WO1994018906 A1 WO 1994018906A1 US 9401734 W US9401734 W US 9401734W WO 9418906 A1 WO9418906 A1 WO 9418906A1
Authority
WO
WIPO (PCT)
Prior art keywords
artificial organ
membrane
housing
εaid
selectively permeable
Prior art date
Application number
PCT/US1994/001734
Other languages
English (en)
Inventor
Anthony P. Monaco
Takashi Maki
Jeremy Peter Alan Lodge
Original Assignee
New England Deaconess Hospital, Corp.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by New England Deaconess Hospital, Corp. filed Critical New England Deaconess Hospital, Corp.
Priority to AU62432/94A priority Critical patent/AU6243294A/en
Publication of WO1994018906A1 publication Critical patent/WO1994018906A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/022—Artificial gland structures using bioreactors

Definitions

  • Semipermeable membranes containing a cell which produces a biologically active substance often are implanted into a subject's body for a variety of purposes.
  • the membrane allows bodily fluids to diffuse in and out of the membrane but prevents the movement of the subject's immune cells into the membrane.
  • implantable semipermeable membranes have been used to immunoisolate parasitic cell or infective larvae in studies relating to the immune response of a host to parasitic infection.
  • Diffusion housings have also been used to study in vivo or in vitro bacterial pathogenesis, e.g., Bordetella pertussis pathogenesis.
  • pancreatic islet cells are enclosed in a semipermeable diffusion membrane which is then implanted in a diabetic mammal. Insulin diffuses through the diffusion membrane and can ameliorate diabetic conditions for limited periods of time. Nutrients diffuse through the membrane to support metabolism of islet cells.
  • Implantable, semipermeable diffusion membranes have a number of disadvantages. Most significantly. implantation of numerous semipermeable membranes such as beads, straws, or discs into a body cavity of a patient in large numbers makes retrieval extremely difficult, if not impossible. In the case of cells with a limited life span, re-implantation of the individual membranes containing fresh cells is very difficult, time-consuming and dangerous to the patient, especially if the membranes become scattered throughout the body cavity by movement of the patient. Furthermore, diffusion membranes are subject to breakage during, and after, the implantation process and during subsequent activity of the patient. Breakage of the membranes can lead to spillage of the enclosed cells, thus exposing the cells to the patient's immune system.
  • the present invention pertains to an artificial implantable organ.
  • the artificial organ includes a first housing having at least one interior and at least one exterior surface.
  • the interior surface(s) define a chamber and the exterior and interior surfaces are in fluid communication with each other. At least a portion of the first housing is accessible to bodily fluids.
  • a membrane is disposed within the chamber, at least a portion of the membrane being selectively permeable to bodily fluids.
  • the membrane contains one or more cells (“cells”) capable of producing a biological agent such as a hormone, cellular growth factor, and the like.
  • the cells are preferably disposed entirely within the confines of the membrane.
  • the first housing is a geometrical shape having interconnected interior surfaces and exterior surfaces. The interior and exterior surfaces in closest facing relationship to each other are perforated.
  • the housing can be arranged to allow bodily fluids to pass transversely through the housing to completely and persistently be in contact with the semipermeable membrane.
  • the selectively permeable membrane allows nutrients in body fluids to pass through it to nourish the contained cells and permits a biological agent produced by the cells to pass through the membrane.
  • the membrane prevents the cells from immunological attack, rejection, or physical escape.
  • the selectively permeable membrane that is disposed within the chamber of the first housing can include a plurality of tubular membranes. In one embodiment of the invention, these tubular membranes are arranged within the chamber in a pinwheel configuration. In another embodiment, a plurality of tubular membranes are arranged parallel to each other within the chamber. Further configurations of the invention include a single, tubular membrane coiled within the chamber. The tubular membrane can also be coiled around a second housing that is concentrically disposed within the chamber of the first housing. Further embodiments include a cellular growth factor disposed within the membrane.
  • a preferred selectively permeable membrane is a tube with closed ends whose total length is substantially greater than any linear dimension of the first housing.
  • the selectively permeable membrane is a closed tube disposed within the chamber of the first housing, the tube having an internal volume that is substantially equal to the internal volume of the chamber.
  • Kits of the invention therefore include loaded and assembled artificial organs.
  • the invention also pertains to methods for delivering a beneficial agent to a body using the artificial organ of the invention.
  • KJLE 26 provide an artificial implantable organ that protects a selectively permeable membrane from breakage during the implantation process.
  • Fig. l is a schematic, cross-section illustration of the implantable artificial organ of the present invention.
  • Fig. 2 is a schematic, top-view illustration of another embodiment of the implantable artificial organ of the invention.
  • Fig. 3 is a cross-sectional view through line A-A of the embodiment of Fig. 2.
  • Fig. 4 is a schematic, top view illustration of another embodiment of the implantable artificial organ of the invention.
  • Fig. 5 is a cross-sectional view through line B-B of the embodiment of Fig. 4.
  • Fig. 6 is an alternate embodiment of Figs. 4 and 5 5 in cross- ⁇ ecticn.
  • Fig. 7 is a schematic, top view illustration of another embodiment of the implantable artificial organ of the invention.
  • Fig. 8 is a partial cut-away view of another embodiment of the implantable artificial organ of the invention.
  • Fig. 9 is a partial cross-sectional view through line C-C of Fig. 8.
  • Fig. 10 is a partial cross-sectional view of an alternate embodiment of Figs. 8 and 9.
  • Fig. 11 is a schematic, cross-sectional illustration of another embodiment of the implantable artificial organ of the invention.
  • the present invention is directed to an artificial organ for implantation into a subject, and processes for implanting and using such organs within the body of the subject.
  • subject in this context refers primarily to humans, although non-human vertebrates such as primates, dogs, cats, horses and the like are also included within the meaning of the term.
  • the implantable artificial organ has the capability of preventing entry of immunologically active substances (i.e. lymphocytes, macrophage ⁇ , circulating antibodies, and the like) into the artificial organ, thus simultaneously housing biologically active cells in the organ and protecting the cells from the immunologically active substances.
  • immunologically active substances i.e. lymphocytes, macrophage ⁇ , circulating antibodies, and the like
  • the artificial organ permits the ingress of nutrients and body fluids therein and permits the egress of waste products and biological agents produced by the biologically active cell from the artificial organ.
  • the result is a viable, ongoing source of a biological agent contained within the artificial organ which functions on a relatively long-term basis without rejection (immunological destruction) by the subject.
  • Fig. 1 illustrates in schematic form a cross-sectional view of the general construction and operation of the present implantable artificial organ.
  • the artificial organ 10 includes a first, three-dimensional housing 12 having at least one exterior surface 14 and at least one interior surface 16.
  • the first housing 12 is a hollow sphere with one interior and exterior surface.
  • the interior surface 16 of the first housing 12 defines a chamber 18.
  • At least a portion of the first housing's exterior 14 and interior 16 surfaces contain perforations 20 that render at least that portion of the first housing accessible to bodily fluids.
  • a membrane 22 is disposed within chamber 18.
  • Membrane 22 includes interior 24 and exterior 26 surfaces. A portion 28 of these surfaces 24,26 is selectively permeable to bodily fluids.
  • the interior surface 24 of membrane 22 defines an internal volume 30, hereinafter referred to as a lumen.
  • One or more biologically active cells 32 (hereinafter “cells”) capable of producing a biological agent are disposed completely within lumen 30 of membrane 22.
  • the interior surface 16 of first housing 12 and exterior surface 26 of membrane 22 define between them a volume 34 that is accessible to bodily fluids. In Fig. 1., volume 34 is also free of the biologically active cells 32.
  • First housing 12 can be compatible with implantation into a living body and can be of sufficient thickness and of sufficient inflexibility to protect membrane 22 from breakage.
  • the first housing 12 can be comprised of, for example, stainless steel, titanium, or other implantable substances, including organic polymers such as a variety of plastics, so long as the material is non-reactive (i.e. biologically inert).
  • the first housing can be polytetrafluoroethylene, silicon-coated plastic, polycarbonate, polysulfone, polymethyl methacrylate or mixtures thereof.
  • the first housing can also be fabricated of woven or fibrous materials, such as, for example Dacron or polytetrafluoroethylene mesh.
  • the term “accessible” refers to a characteristic of at least part of the first housing 12 that allows bodily fluids to be in fluid communication with the housing without any restrictions or molecular size exclusions.
  • the term “accessible” particularly refers to fluid communication that relies on passive movement of bodily fluids and is not meant to include fluid communication based upon connection of the artificial organ to blood vessels and/or lymph ducts for active pumping of fluids through the artificial organ.
  • Bodily fluids means plasma, blood, lymph, urine, salts, gases, metabolic products, solutes, cell cytoplasm, and other liquid and gaseous materials found within the body of a subject.
  • Accessibility to bodily fluids of the first housing 12 is effected by the presence of a plurality of perforations 20 that will allow the passive entrance and exit of bodily fluids.
  • the perforations can include a variety of shapes and configurations.
  • the perforations can be of any size, so long as the membrane 22 is protected from physical damage by adjacent body organs or cells.
  • the first housing 12 has a plurality of perforations 20 of substantially circular cross section, each perforation consisting essentially of a thin tube extending from exterior surface 14 to the interior surface 16 of the first housing 12.
  • the perforations may include an interconnected matrix of substantially tubular pores.
  • the perforations 20 of first housing 12 are configured in a grid or mesh work configuration and include a lattice of overlapping and/or interconnected mesh.
  • membrane 22 is a thin sheet or layer. At least a part of the membrane is selectively permeable.
  • selectively permeable refers to membranes characterized in their ability to permit entry only of a certain kind and
  • a selectively permeable membrane 22 should bar components of the cell-mediated and humoral immunological responses, i.e., macrophages, complement, lymphocytes and antibodies from entry into the membrane while allowing the passage of bodily fluids (i.e. salts, blood plasma, blood, lymph, growth factors, nutrients, gases, metabolic breakdown products, solutes) and the biological agent produced by the cells to pass therethrough.
  • bodily fluids i.e. salts, blood plasma, blood, lymph, growth factors, nutrients, gases, metabolic breakdown products, solutes
  • bodily fluids can pass into the membrane 22 and interact with the cells contained within the membrane. Any biological agent(s) released by the cells will exit membrane 22, pass through chamber 18, out of the housing 12 and be released into the body.
  • Fig. 1 illustrates a three-dimensional membrane 22 completely enclosing cells 32
  • membrane 22 can also contain cells 32 that are embedded or otherwise impregnated into the membrane material itself.
  • cells 32 can be supported on the interior surface 24; and/or between interior and exterior 26 surfaces.
  • the permeability of the membrane is a function of the composition of the particular materials used.
  • any biologically inert material i.e. incapable of initiating a biological reaction, such as an immune response, in the recipient subject
  • perforations referred to in this context as "pores"
  • pores enabling passage of molecules with a molecular weight of between about 50,000-80,000 Dalton ⁇
  • the membrane is a porous acrylic copolymer membrane of about 50,000-80,000 Dalton average porosity such as the type XM manufactured by the Amicon Division of W.R. Grace and Company.
  • the pore sizes of the preferred membranes are selected to provide a barrier to protect the cells from a host immune reaction.
  • the appropriate pore size can be determined u ⁇ ing no more than routine methods. For example, the pore size can be ⁇ elected . on the basis that the membrane must exclude greater than 90 percent of an IgG solution.
  • thi ⁇ membrane Because of thi ⁇ membrane, cells from a variety of source ⁇ can be implanted in a recipient subject without necessarily requiring drug-induced immune suppression of the recipient subject.
  • the membrane can be made in a variety of preferred
  • the lumen 30 of the membrane 22 can preferably range from about 0.02 to about 100 cubic centimeters and the effective distance between cells inside the membrane and the exterior surface of the first housing is preferably no greater than about 3.0 centimeters.
  • the membrane will be in the shape of a hollow tube or bag whose ends are sealed together u ⁇ ing adhe ⁇ ive ⁇ , heat, ultrasound and the like.
  • An important feature of the present invention is that the membrane i ⁇ de ⁇ igned to minimize the area of its sealed edges relative to its total surface area. In this way, the amount of sealed surfaces in contact with the environment of use is minimized.
  • the epoxy resins may volatilize and/or release unde ⁇ irable compound ⁇ into the environment of use.
  • manipulation and fabrication of the present implantable organ ⁇ is simplified if the membranes are made with as few sealed edges as po ⁇ ible. Preferred con ⁇ truction ⁇ of the membrane de ⁇ igned to minimize the ⁇ ealed ⁇ urface area will be pre ⁇ ented in more detail below.
  • cells 32 are contained within lumen 30 of membrane 22.
  • Cells that are thus encapsulated and implanted may be "allografts, " or cells implanted one member of a species to another of
  • J3STITUTE SHEET RULE 26 the same species as the subject in which they are to be implanted, or they may be "xenografts" , or those from another of a different specie ⁇ . More particularly, they may be a component (i.e. a portion or con ⁇ tituent) of a body organ which normally ⁇ ecretes a particular biological agent in vivo.
  • the cells are desirably used as single, dispersed cells or in cell aggregate form.
  • the actual cell size and the quantity of cells in the device of the present invention will depend to a significant degree on a correlation of various factors such as the chemical composition of the hou ⁇ ing, membrane configuration, the construction of the device, the cells of choice, the disease to be treated, ameliorated or controlled, the environment of use including nutrients available for generating or promoting formation of a biological agent, and other considerations.
  • the artificial organ will contain a quantity of cells at least sufficient to produce a biological agent that effects a desired result, and/or treats, ameliorates and/or controls a targeted disease.
  • cells include cells from the thyroid (thyroid hormone), parathyroid (parathormone) , adrenal gland (adrenalin, gluco-corticoids, steroid ⁇ ), nerve cell ⁇ (nerve growth factor ⁇ ), liver cell ⁇ (enzymes or coagulation proteins) .
  • the term "cell ⁇ " can also include whole cell aggregates and can also include microorgani ⁇ ms ⁇ uch a ⁇ bacteria and protozoan ⁇ , capable of producing one or more biological agent ⁇ .
  • genetically engineered cells and cell ⁇ modified by conjugation, hybrid DNA or fusion can be used. See, for example, Kawakami et al. Diabetes 41:956-961 (1992); McGerty, K. , "Prospects For Gene Therapy And Cellular Engineering In Diabetes,' pp. 154-182 in Biotechnology of Insulin Therapy, (ed. J.C. Pickup), Blackwell, London (1991), incorporated herein by reference.
  • cell types which can grow in suspension culture, as well a ⁇ anchorage- dependent cells can be used in this invention. Specific examples include fibroblast ⁇ , leukocyte ⁇ , ly phobla ⁇ toid ⁇ , pituitary cell ⁇ , and the like.
  • cells can include cell fragments, cell clumps and single cell ⁇ . It will thu ⁇ be appreciated that the biological agent can augment activity of an organ within the body of a ⁇ ubject, which organ ha ⁇ lo ⁇ t it ⁇ ability, or has a diminished capacity, to produce a biological agent.
  • the proce ⁇ and apparatus of thi ⁇ invention i ⁇ particularly suitable for using pancreatic endocrine cell from pancreatic i ⁇ let ⁇ or islet cell ⁇ for implantation into the body and for release of insulin.
  • pancreatic islet cell ⁇ for thi ⁇ function are ⁇ ub ⁇ tantially fibrobla ⁇ t-free cell preparation ⁇ derived from cultured fetal i ⁇ let cells or intact, whole organ pancreas, which are subsequently cultured _in vitro.
  • pancreatic islet cells derived from cultured fetal i ⁇ let cells or intact, whole organ pancreas, which are subsequently cultured _in vitro.
  • the invention will be described hereinafter in terms of pancreatic islet cells, it being understood the proce ⁇ and product i ⁇ al ⁇ o suitable for implanting other types of cell ⁇ , a ⁇ de ⁇ cribed above.
  • the ⁇ e other types can be considered alternates in the invention
  • the concentration of islet cell ⁇ within the membrane can be from about 10 2 to 108 cells/ml.
  • pancreatic i ⁇ let cell ⁇ ⁇ uitable for incorporation into the membrane of this invention can be derived from pancreatic cell by numerous published procedures or they can be derived from cell, organ or cell cultures.
  • pancreatic islets includes the con ⁇ tituent cell type ⁇ within the islet of Langerhans including beta cells, the actual producers of insulin, intact islets, islet fragments, genetically engineered islet cells or combinations of the foregoing. A procedure for i ⁇ olating i ⁇ let ⁇ from a donor pancrea ⁇ i ⁇ described in Example 1.
  • the islet materials can also contain other cell which enhance islet viability.
  • the presence of endothelial cell ⁇ or fibroblasts can create an environment more like that in which i ⁇ let cells naturally occur.
  • Other cell types which produce growth factors and/or soluble, cellular growth factor ⁇ or basement membrane components can be cultured with the islet ⁇ and included within the membrane to enhance growth and viability.
  • Figs. 2 and 3 illustrate one embodiment of the artificial organ of the present invention.
  • the first housing 12 is a geometrical shape with a plurality of interconnected exterior 17 and interior 15 surfaces.
  • the first housing 12 is a toroidal or donut configuration. It will be appreciated that a disc, square, cylinder or rectangular shape will al ⁇ o be ⁇ uitable.
  • SHEET(RULE 26) has two interior 15 and exterior 17 surfaces in clo ⁇ e ⁇ t facing relationship to each other. These particular surface ⁇ contain perforation ⁇ 20 and are acce ⁇ sible to bodily fluids. Interior surface ⁇ of the first hou ⁇ ing 12 define chamber 18. Becau ⁇ e housing 12 is designed ⁇ o that the ⁇ urfaces in close ⁇ t facing relation ⁇ hip to each other are acce ⁇ ible to bodily fluid ⁇ , the housing will allow bodily fluids to pass transversely through it.
  • transver ⁇ ely refer ⁇ to bidirectional flow (shown by the double-headed arrows in Fig.
  • Perforations 20 on first housing 12 thus allow bodily fluid ⁇ to flow between the surface ⁇ that are in close ⁇ t facing relation ⁇ hip to each other (i.e. "transversely” through the hou ⁇ ing) .
  • the perforation ⁇ 20 of the first housing can be of any shape or dimension, provided that they are smaller than the width (W) of the enclosed membranes 22, to prevent the membrane from escaping out of the first housing.
  • a plurality of selectively permeable membranes 22 is completely enclosed within chamber 18 of first housing 12.
  • the membranes 22 are a plurality of tubular, selectively permeable membranes with closed ends 38, the membranes 22 being arranged in a pinwheel configuration within chamber 18.
  • Each membrane of the pinwheel contains cell ⁇ 32 for producing a biological agent.
  • each individual membrane 22 i ⁇ spaced apart from an adjacent membrane by between l-5mm and each individual membrane is arranged radially around a central, membrane-free region 40 of the first hou ⁇ ing 12.
  • the length of the individual membrane ⁇ can range from about 1.0 to about 5.0 cm.
  • the width of each individual membrane 22 can range from about 0.05 cm to about 1.5 cm. Most preferably, the membranes are about 1.0-5.0 cm long by about 0.5 cm wide.
  • the number of membranes will depend upon the size of the first housing 12 and the spacing between individual membrane ⁇ . Significantly the number of membrane ⁇ in this embodiment, as in the other embodiments, will also be determined by the patient requirement for the biological agent. In the case of diabetes, for example, the number of membranes can be ea ⁇ ily altered to provide a calibrated amount (e.g. 15, 30, 40 Units) of insulin for delivery.
  • the individual membranes can be tethered to each other u ⁇ ing a biocompatible ⁇ uture material or attached to an interior surface 15 of the first housing 12. Nevertheless, it is preferred that the individual membranes 22 not be bound together or be affixed to the in ⁇ ide of the first hou ⁇ ing. Rather, a ⁇ illu ⁇ trated in Fig ⁇ . 2 and 3, small section ⁇ of inert material 42 (hereinafter called " ⁇ pacer ⁇ ”) are constructed to protrude from interior surface 15 of the first housing 12. Spacers 42 physically separate individual membrane ⁇ 22 and facilitate circulation of bodily fluid ⁇ between membranes. The projection of the ⁇ pacer ⁇ into the housing can vary so long a ⁇ they
  • first housing 12 i.e., the distance between those perforated sides in close ⁇ t facing relation ⁇ hip to each other
  • i ⁇ designed so that tran ⁇ verse movement of the membranes within chamber 18 is severely constrained.
  • the depth of the hou ⁇ ing i ⁇ substantially equal to the width (W) of the membranes.
  • the size of a typical toroidal first housing 12 ranges from about 3.0 cm in diameter to about 10.0 cm in diameter with a depth of about 1.5 cm. Most preferably, the first hou ⁇ ing shown in Fig ⁇ . 2 and 3 range ⁇ from about 3.0 to about 8.0 cm in diameter.
  • Figs. 4 and 5 illustrate yet another embodiment of the artificial organ.
  • the first housing 12 i ⁇ substantially rectangular in shape.
  • the interior 15 and exterior 17 surface ⁇ in clo ⁇ e ⁇ t facing relation ⁇ hip to each other contain perforation ⁇ 20.
  • Interior surfaces 15 define chamber 18.
  • a plurality of selectively permeable, ⁇ ub ⁇ tantially tubular membrane ⁇ 22 are disposed within chamber 18 and are arranged in parallel.
  • the membranes have closed ends 38.
  • Membranes 22 can be arranged to have a length (L) equal to a linear dimension (i.e., width or length) of the first hou ⁇ ing, depending upon which orientation the membrane ⁇ are placed.
  • Each of the individual membrane ⁇ 22 contain cell ⁇ 32 and each membrane i ⁇ separated from adjacent membranes by ⁇ pacer ⁇ 42 projecting from an interior ⁇ urface 15 of the fir ⁇ t hou ⁇ ing. Movement of the individual membranes 22 within chamber 18 i ⁇ constrained by the dimensions of the chamber. That i ⁇ , the width (W) of any membrane ⁇ will be sub ⁇ tantially identical to the depth of the first housing.
  • a rectangular first hou ⁇ ing 12 of about 8.0 cm x 4.5 cm wide x 0.5 cm in depth i ⁇ ⁇ uitable for implantation in, for example, the abdominal cavity.
  • the membrane can be about 8.0 cm long x about 0.5 cm wide.
  • Figure 6 illu ⁇ trates an alternate embodiment with two layers of membranes. Reference numbers are identical to Fig. 5, except where indicated.
  • a first housing 12 has a depth of about 1.0 cm, so that a second layer of membranes 46 is superimposed on top of the first layer of membranes 22.
  • spacer ⁇ 48 are provided to separate the superi po ⁇ ed layers of membranes 22 and 46.
  • Spacers 48 preferably traverse the inside of the first housing 12 either along its length, its width, or along both (e.g. in a cris ⁇ -cross configuration) .
  • Fig. 7 illu ⁇ trates another embodiment of the artificial organ, showing a significant feature of the present invention; namely that the membrane is constructed to minimize the numbers of its sealed ends and maximize its total surface area.
  • a ⁇ ubstantially disc-like first hou ⁇ ing 12 completely encloses a tubular, selectively permeable membrane 22 whose length i ⁇ ⁇ ub ⁇ tantially greater than any linear dimension of the first housing.
  • the membrane 22 i ⁇ a single, coiled tube containing cells 32. It will be readily appreciated that the ⁇ urface ⁇ available for ⁇ ealing the membrane are limited to the end ⁇ 38 of the coiled membrane 22. Thi ⁇ i ⁇ but one construction that will minimize the ratio: number ⁇ of sealed ends/total ⁇ urface area of the membrane.
  • An interior ⁇ urface 15 of fir ⁇ t hou ⁇ ing 12 define ⁇ chamber 18.
  • Interior surface 15 has a central projection 50. Emanating radially outwardly from the central projection are a variety ⁇ of ⁇ pacers 42, also protruding from surface 15.
  • the ⁇ e ⁇ pacer ⁇ 42 separate the coils of the tubular membrane 22 from each other a ⁇ it is wound within chamber 18 of housing 12.
  • the first housing has interior 15 and exterior 17 surfaces in closest facing relationship to each other that contain perforations 20.
  • a preferred first housing is a disk about 8.0 cm in diameter x 0.5 cm in depth.
  • the width (W) of the preferred single, coiled membrane 22 can be ⁇ ub ⁇ tantially equal to the depth of the fir ⁇ t hou ⁇ ing.
  • the membrane 22 can be of any length; long length ⁇ are ea ⁇ ily obtainable by winding the membrane around the central projection 50 in progre ⁇ ively larger coil ⁇ . It will be under ⁇ tood that more than one coiled membrane can be accommodated within the fir ⁇ t hou ⁇ ing as two or more layers. The number of such membranes (layers) will depend primarily upon the width of the membranes(s) and the depth of the fir ⁇ t housing.
  • the artificial organ includes a pair of concentrically arranged housings that are acces ⁇ ible to bodily fluid ⁇ .
  • the housings can be of any shape (i.e. square, circular, rectangular, and the like).
  • Mo ⁇ t preferably, the concentrically arranged hou ⁇ ing ⁇ are cylindrical.
  • an outer, fir ⁇ t housing 100 i ⁇ a cylinder with a diameter of between about 3 and 4 centimeter ⁇ and a height of between about 6 to 10 centimeter ⁇ .
  • a second, inner cylindrical housing 105 i ⁇ di ⁇ po ⁇ ed in chamber 106, the chamber 106 defined by the interior ⁇ urface ⁇ 110 of the fir ⁇ t cylindrical housing 100.
  • the first cylindrical housing 100 has exterior surfaces 115.
  • the second cylindrical housing 105 also ha ⁇ interior 120 and exterior 125 surfaces.
  • a substantially annular volume 130 is defined between the interior surface.110 of first housing 100 and exterior surface 125 of second housing 105. Di ⁇ po ⁇ ed within volume 130 i ⁇ a ⁇ electively permeable membrane 135.
  • the selectively permeable membrane 135 is wound around the exterior surface 125 of the ⁇ econd, inner hou ⁇ ing 105 a ⁇ a plurality of coils, the coil ⁇ ⁇ eparated from each other by a ⁇ pacer (al ⁇ o in the ⁇ hape of a coil) 150 that i ⁇ ⁇ upported on the exterior ⁇ urface 125 of the second, inner housing 105.
  • Cells 155 capable of releasing a biological agent are dispo ⁇ ed within the selectively permeable membrane 135.
  • the exterior and interior surfaces of both the cylinders preferably include perforations 160.
  • the end ⁇ 165 of the fir ⁇ t, outer housing 100 and the end ⁇ 170 of the second, inner housing 105 also include perforation ⁇ 160 (end perforations are shown only for the interior housing in Fig. 8) .
  • the perforations 160 of the two cylindrical housings 100, 105 allow bodily
  • Fig. 9 illu ⁇ trate ⁇ a partial cro ⁇ - ⁇ ection through line C-C of Fig. 8, with identical reference number ⁇ being u ⁇ ed, except where indicated.
  • the total length of membrane 135 i ⁇ the ⁇ um of number of coils x the length of each coil, where the length of each coil i ⁇ diameter of the inner housing 105.
  • the width (W) of the annular volume 130 i.e. the distance between the respective ⁇ urface ⁇ 110, 125 of the two cylindrical hou ⁇ ing ⁇
  • i ⁇ preferably ⁇ ub ⁇ tantially equal to the diameter of the selectively permeable membrane 135.
  • the second, inner housing i ⁇ not fixed to the fir ⁇ t, outer hou ⁇ ing. That i ⁇ , neither exterior ⁇ urface 125, nor end ⁇ 170 of the ⁇ econd, inner hou ⁇ ing 105 are attached to the outer housing 100. It will, however, be understood that one, or both, ends 170 of the second, inner housing 105 can be affixed to the respective end ⁇ 165 of the fir ⁇ t, outer hou ⁇ ing 100 without departing from the scope of the invention.
  • FIG. 10 illu ⁇ trate ⁇ an alternate embodiment of Fig ⁇ . 8 and 9 in which inner housing 105 i ⁇ integral with an end 165 of outer hou ⁇ ing 100.
  • Inner hou ⁇ ing 105 lack ⁇ a ⁇ eparate perforated end ⁇ ection ⁇ o that interior 120 and exterior 125 surfaces of inner housing 105 abut directly against end 165 of the outer hou ⁇ ing 100. All reference numbers are identical to those in Fig ⁇ . 8 and 9.
  • FIG. 11 illustrates yet another embodiment of the invention.
  • a substantially disc-shaped fir ⁇ t housing 12 is shown, with interior and exterior surface ⁇ 15, 17, respectively, in closest facing relationship to each other containing perforations 20 and being acce ⁇ ible to bodily fluids.
  • the membrane 22 define ⁇ a lumen 30 that takes up almost the entire chamber volume.
  • the lumen 30 of membrane 22 can have a volume from about 1% to about 5% smaller than the volume of chamber 18.
  • the sealed edges 38 of membrane 22 are ⁇ hown in the cro ⁇ -sectional view. It will be appreciated that the ratio of the ⁇ ealed ⁇ urface area of the member to the total ⁇ urface area of the membrane is also at a minimum in this particular configuration.
  • the artificial organ of the pre ⁇ ent invention can include one or more first hou ⁇ ing ⁇ ⁇ tacked together as a unit, each of the first
  • SHEET(RULE 26) housing ⁇ containing a membrane enclo ⁇ ing cell ⁇ , a ⁇ described herein.
  • the membrane can be impregnated or filled with a cellular growth factor or other material to enhance growth of the enclosed surrounding cell ⁇ .
  • Growth factor ⁇ or other agents such as angiogenic factors, interleukin ⁇ , chemotactic factor ⁇ , and the like are well known to those of ordinary skill in the art.
  • a matrix of collagen or other structural material can be incorporated within the membrane ⁇ .
  • Thi ⁇ matrix would allow growth of capillarie ⁇ which may provide additional nouri ⁇ hment for the cell ⁇ within the membrane ⁇ .
  • the artificial organ ⁇ of the present invention can be ea ⁇ ily fabricated using conventional methods.
  • Metallic housing ⁇ can be fabricated u ⁇ ing conventional milling procedure ⁇ . If pla ⁇ tic, hou ⁇ ing ⁇ can be made u ⁇ ing conventional lamination, extru ⁇ ion and/or molding procedure ⁇ . Perforation ⁇ can be drilled or incorporated in a mold.
  • the first housings are fabricated a ⁇ open di ⁇ c ⁇ or boxe ⁇ with no top. The depth of the box plu ⁇ the top i ⁇ about equal to, or only ⁇ lightly larger than, the width of the membrane that is to be placed in the first hou ⁇ ing.
  • the membranes are loaded with cell, sealed, and then placed within the first housing.
  • the presence of ⁇ pacer ⁇ on the interior surfaces of the first housing aid ⁇ in the correct po ⁇ itioning of the membrane( ⁇ ) .
  • the toroid is fabricated with a central core, sidewall ⁇ , and no top.
  • U ⁇ c cuf-TT (RULE 26 including top, is approximately 1-5 mm larger than the width of the membrane ⁇ .
  • the interior ⁇ urface of the toroid ha ⁇ ⁇ pacer ⁇ protruding from it and the membrane ⁇ are placed in between the ⁇ pacer ⁇ .
  • Each membrane ha ⁇ two ⁇ ealed end ⁇ abutting the outer periphery of the toroid at their one end, and the interior central core of the toroid at their other end.
  • the fir ⁇ t housing is constructed essentially like a cigar box without a top and with a depth slightly greater than the width of the individual membrane ⁇ .
  • the membrane is of length equal to a linear dimension of the first housing (i.e., width or length) depending upon the way the membrane ⁇ are placed.
  • the interior ⁇ urface of the fir ⁇ t hou ⁇ ing include ⁇ ⁇ pacer ⁇ to separate the membranes from each other.
  • the fir ⁇ t housing is closed by attaching a lid with epoxy or screws, as with the previou ⁇ embodiment.
  • the ⁇ pace between the membrane ⁇ is formed by the spacer ⁇ in order to provide free flow of bodily fluid around the membrane.
  • Fig. 7 the configuration embodied therein i ⁇ ⁇ ub ⁇ tantially a circular pill box with no top and a central po ⁇ t po ⁇ itioned on a interior ⁇ urface of the pill box. Emanating from the central po ⁇ t are ⁇ pacers which separate the coils of the membrane at equal intervals a ⁇ the membrane is wound around the central post. The membrane is filled with the appropriate pancreatic islet ⁇ and the end ⁇ of the membrane are ⁇ ealed. The membrane i ⁇ then be wound around the central post in between the ⁇ pacer ⁇ . A top of the fir ⁇ t hou ⁇ ing i ⁇ placed on the pill box with epoxy or screw ⁇ , a ⁇ described above. Alternatively, the membrane can be ⁇ ealed at one end, wound around the central po ⁇ t, and then filled and ⁇ ealed while it i ⁇ in the open pill box. Then, the top i ⁇ placed on the open pill box.
  • the concentrically arranged cylinder ⁇ of Figure ⁇ 8-10 i ⁇ a ⁇ embled in a similar manner.
  • the membrane is filled with the appropriate pancreatic islets and the ends of the membrane are sealed.
  • the membrane i ⁇ then be wound around the inner hou ⁇ ing in between the ⁇ pacer ⁇ .
  • the membrane can be sealed at one end, wound around the inner hou ⁇ ing, and then filled and sealed while it is in the open outer hou ⁇ ing. Then, the end is placed on the outer housing.
  • the invention also pertains to artificial organ kit ⁇ u ⁇ ed for ea ⁇ e of ⁇ urgical operation ⁇ .
  • the kit contain ⁇ a membrane filled with a biologically active cell (i.e. pancreatic i ⁇ let cells).
  • the membrane i ⁇ contained within the fir ⁇ t hou ⁇ ing, a ⁇ de ⁇ cribed herein and completely assembled, either in the operating room immediately pre-operation, or as ⁇ embled in a laboratory and ⁇ hipped to the operating room in a ⁇ terile container.
  • Sterilization u ⁇ ing for example, ethylene oxide, and methods of shipping and packing medical devices to maintain sterility are well-known to those workers of ordinary skill in the art.
  • the implantable artificial organ of the pre ⁇ ent invention can be placed in any body cavity.
  • the preferred location within a preferred ⁇ ubject i.e. a mammal such a ⁇ a human
  • i ⁇ the peritoneal cavity The mo ⁇ t preferred location in human subjects is in the lower abdominal cavity; in the area called the "anatomic pouch of Douglas".
  • the artificial organ of the invention i ⁇ placed in the "pouch of Dougla ⁇ " and allowed to be pa ⁇ oively bathed with bodily fluid in the abdominal cavity. About 500 cc's of saline solution is added to the pouch area so that the artificial organ housing i ⁇ well bathed initially.
  • the artificial organ is placed in a body cavity of a subject by a lower abdominal mid-line incision performed under local anesthe ⁇ ia. This involves, at best, day surgery, i.e. the patient comes in the morning, ha ⁇ the placement done, and i ⁇ allowed to go home on the same day.
  • the length of the lower abdominal mid-line incision i ⁇ determined by the maximum diameter or length of the fir ⁇ t housing.
  • a fir ⁇ t housing can be made ⁇ mall enough ⁇ o that it could be inserted by laparoscopic technique ⁇ .
  • Thi ⁇ can be done if the fir ⁇ t housing i ⁇ constructed as a rectangle with a measurement of perhaps 2 or 3 cm by 6 or 8 cm.
  • the functioning of the implantable artificial organ can be easily tested by monitoring bodily fluids of the ⁇ ubject for the particular beneficial agent expected to be produced by the cell. Increases in levels over "background" (i.e. preimplantation) indicate the implantable organ is functioning.
  • the placement of the artificial organ of the invention in the human body must have the possibility of being completely removed, retrieved, and/or recharged and reimplanted utilizing relatively simple methods. If one were to have membrane ⁇ by them ⁇ elve ⁇ in the abdominal cavity in multiple number ⁇ , i.e. 50, 100 or 200 membrane ⁇ , the chance ⁇ of retrieving them completely and easily would be extremely difficult.
  • Membranes, enclo ⁇ ed within, and protected by, a fir ⁇ t hou ⁇ ing makes retrievability of the artificial organ very easy.
  • the housing ⁇ would be removed and po ⁇ ibly re-implanted with fresh cells the same way they were placed, i.e. through a lower mid-line abdominal incision performed under local anesthesia. Placement or removal of the artificial organ in the pouch of Douglas can be a ⁇ imple operation of very ⁇ hort duration.
  • the artificial organ ⁇ are ideal for placement in the abdominal pouch of Dougla ⁇ in that their configuration and their weight maintain the artificial organ hou ⁇ ing in the pouch area.
  • the artificial organ can al ⁇ o be anchored in the pouch of Dougla ⁇ by a ⁇ ingle suture or two to the posterior parietal peritoneum.
  • ea ⁇ e of placement, ⁇ ecurity of placement, and anchoring of placement in thi ⁇ area are advantage ⁇ inherent in the pre ⁇ ent invention. Since the artificial organ i ⁇ preferably located in that portion the of the body where peritoneal fluid collect, becau ⁇ e of dependency (i.e. being the lowe ⁇ t portion), the device i ⁇ continually bathed in bodily fluid ⁇ .
  • the artificial organ of the invention al ⁇ o protect ⁇ the membrane ⁇ from being broken while in the body and therefore protect ⁇ their integrity from a possible immune rejection from the body's immunological reactivity.
  • Mo ⁇ t prior art diffu ⁇ ion membrane configuration ⁇ are such that the membrane i ⁇ ea ⁇ ily breakable because of torque or twisting impo ⁇ ed on the membrane ⁇ when they move around freely in the abdominal cavity. Since the membranes of the pre ⁇ ent artificial organ are prevented from movement and protected from outside pres ⁇ ure ⁇ , the likelihood of them breaking is es ⁇ entially zero.
  • Islets of Langerhans are obtained from the pancreas of donor animals (e.g. dog, cattle, pig) . Islet ⁇ of Langerhans are isolated and purified by modifications of published procedures. See, Gotoh et al.. Transplantation, 40(4) :437-438 (1985). Briefly, an intact pancreas is infused by way of the pancreatic duct with a suspension of collagenase which dige ⁇ t ⁇ connective ti ⁇ ue and di ⁇ rupt ⁇ the integrity of the gland.
  • a me ⁇ h filter opening 860 microns, Bellco, Vineland, NJ
  • Islet ⁇ are then ⁇ eparated from non-i ⁇ let cell by centrif gation (800g for about 10 minute ⁇ ) on a di ⁇ continuou ⁇ gradient of Ficoll (Pharmacia Fine Chemical ⁇ , Inc.) (23% w/v; 20.5% w/v; and 11% w/v) , which utilize ⁇ the difference in den ⁇ ity of cell type ⁇ to permit i ⁇ let ⁇ to be po ⁇ itioned at the interface of the 11% and 20.5% Ficoll layer ⁇ . I ⁇ let ⁇ are collected, wa ⁇ hed and plated into culture plate ⁇ until u ⁇ ed.
  • Ficoll Pulcoa Fine Chemical ⁇ , Inc.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Transplantation (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Vascular Medicine (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Prostheses (AREA)

Abstract

L'invention se rapporte à des organes artificiels implantables destinés à l'apport d'un agent biologique à partir de cellules implantées dans la cavité du corps d'un patient. Ces cellules (32) sont maintenues dans une membrane à perméabilité sélective (22), qui permet à l'agent de la traverser tout en interdisant aux globules blancs (immunocytes), aux anticorps et autres agents nocifs présents dans l'environnement d'avoir accès aux cellules. Cette membrane est entièrement entourée d'une enveloppe perforée (12) qui la protège contre toute rupture et qui permet aux liquides biologiques d'entrer en contact étroit avec la membrane. Des organes artificiels implantables sont également décrits, dont tous peuvent être récupérés à partir du sujet, remplacés, ou rechargés et réimplantés.
PCT/US1994/001734 1993-02-18 1994-02-18 Organe artificiel implantable WO1994018906A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU62432/94A AU6243294A (en) 1993-02-18 1994-02-18 Implantable artificial organ

Applications Claiming Priority (2)

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US1904193A 1993-02-18 1993-02-18
US08/019,041 1993-02-18

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5534025A (en) * 1993-06-08 1996-07-09 The Governors Of The University Of Alberta Vascular bioartificial organ
EP0901796A2 (fr) * 1997-09-03 1999-03-17 Circe Biomedical, Inc. Dispositif d'encapsulation
US6023009A (en) * 1996-02-23 2000-02-08 Circe Biomedical, Inc. Artificial pancreas
FR2820057A1 (fr) * 2001-01-30 2002-08-02 Ct De Transfert De Technologie Membrane pour chambre d'encapsulation de cellules produisant au moins une substance biologiquement active et organe bio-artificiel comprenant une telle membrane
EP2305321A1 (fr) 2000-11-17 2011-04-06 Advanced Bio Prosthetic Surfaces, Ltd. Dispositif pour l'administration in vivo d'agents bioactifs et son procédé de fabrication
WO2012010767A1 (fr) 2010-07-22 2012-01-26 Statice Sante Poche pour former un organe artificiel implantable
EP3003215A4 (fr) * 2013-06-07 2017-02-22 The Regents of the University of California Dispositif de greffe et procédé d'utilisation
EP3428264A1 (fr) 2017-07-12 2019-01-16 Defymed Poche non pliable pour former un organe artificiel implantable

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1479002A (en) * 1973-06-06 1977-07-06 Spielberg T Artificial gland structure
US4479796A (en) * 1982-11-15 1984-10-30 Medtronic, Inc. Self-regenerating drug administration device
EP0188309A2 (fr) * 1985-01-03 1986-07-23 Connaught Laboratories Limited Microencapsulation de cellules vivantes
EP0195577A2 (fr) * 1985-03-14 1986-09-24 The Regents Of The University Of California Transplants revêtus et leur procédé de préparation
WO1987003802A2 (fr) * 1985-12-20 1987-07-02 Schrezenmeir Juergen Dispositif et instrument de reception et d'introduction de tissus dans le corps humain
WO1991000119A1 (fr) * 1989-06-30 1991-01-10 Baxter International Inc. Dispositif implantable
US5026365A (en) * 1987-04-29 1991-06-25 The University Of Massachusetts Method and apparatus for therapeutically treating immunological disorders and disease states
WO1993000128A1 (fr) * 1991-06-28 1993-01-07 Brown University Research Foundation Dispositif d'implant neuronal renouvelable et procede d'utilisation
WO1993002635A1 (fr) * 1991-07-30 1993-02-18 Baxter International Inc. Implant foramine

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1479002A (en) * 1973-06-06 1977-07-06 Spielberg T Artificial gland structure
US4479796A (en) * 1982-11-15 1984-10-30 Medtronic, Inc. Self-regenerating drug administration device
EP0188309A2 (fr) * 1985-01-03 1986-07-23 Connaught Laboratories Limited Microencapsulation de cellules vivantes
EP0195577A2 (fr) * 1985-03-14 1986-09-24 The Regents Of The University Of California Transplants revêtus et leur procédé de préparation
WO1987003802A2 (fr) * 1985-12-20 1987-07-02 Schrezenmeir Juergen Dispositif et instrument de reception et d'introduction de tissus dans le corps humain
US5026365A (en) * 1987-04-29 1991-06-25 The University Of Massachusetts Method and apparatus for therapeutically treating immunological disorders and disease states
WO1991000119A1 (fr) * 1989-06-30 1991-01-10 Baxter International Inc. Dispositif implantable
WO1993000128A1 (fr) * 1991-06-28 1993-01-07 Brown University Research Foundation Dispositif d'implant neuronal renouvelable et procede d'utilisation
WO1993002635A1 (fr) * 1991-07-30 1993-02-18 Baxter International Inc. Implant foramine

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5534025A (en) * 1993-06-08 1996-07-09 The Governors Of The University Of Alberta Vascular bioartificial organ
US6023009A (en) * 1996-02-23 2000-02-08 Circe Biomedical, Inc. Artificial pancreas
EP0901796A2 (fr) * 1997-09-03 1999-03-17 Circe Biomedical, Inc. Dispositif d'encapsulation
EP0901796A3 (fr) * 1997-09-03 2000-09-13 Circe Biomedical, Inc. Dispositif d'encapsulation
US8128690B2 (en) 2000-11-17 2012-03-06 Advanced Bio Prosthetic Surfaces, Ltd. Endoluminal device for in vivo delivery of bioactive agents
US10327925B2 (en) 2000-11-17 2019-06-25 Vactronix Scientific, Llc Endoluminal device for in vivo delivery of bioactive agents
US8697175B2 (en) 2000-11-17 2014-04-15 Advanced Bio Prosthetic Surfaces, Ltd., A Wholly Owned Subsidiary Of Palmaz Scientific, Inc. Endoluminal device for in vivo delivery of bioactive agents
EP2305321A1 (fr) 2000-11-17 2011-04-06 Advanced Bio Prosthetic Surfaces, Ltd. Dispositif pour l'administration in vivo d'agents bioactifs et son procédé de fabrication
US8252044B1 (en) 2000-11-17 2012-08-28 Advanced Bio Prosthestic Surfaces, Ltd. Device for in vivo delivery of bioactive agents and method of manufacture thereof
FR2820057A1 (fr) * 2001-01-30 2002-08-02 Ct De Transfert De Technologie Membrane pour chambre d'encapsulation de cellules produisant au moins une substance biologiquement active et organe bio-artificiel comprenant une telle membrane
US7056726B2 (en) 2001-01-30 2006-06-06 Association Pour Les Transferts De Technologies Du Mans membrane for encapsulation chamber of cells producing at least a biologically active substance and bioartificial organ comprising same
WO2002060409A1 (fr) * 2001-01-30 2002-08-08 Association Pour Les Transferts De Technologies Du Mans Membrane pour chambre d'encapsulation de cellules produisant au moins une substance biologiquement active et organe bio-artificiel comprenant une telle membrane.
FR2962898A1 (fr) * 2010-07-22 2012-01-27 Statice Sante Poche pour former un organe artificiel implantable
WO2012010767A1 (fr) 2010-07-22 2012-01-26 Statice Sante Poche pour former un organe artificiel implantable
US8834979B2 (en) 2010-07-22 2014-09-16 Statice Sante Bag for forming an implantable artificial organ
EP3003215A4 (fr) * 2013-06-07 2017-02-22 The Regents of the University of California Dispositif de greffe et procédé d'utilisation
EP3428264A1 (fr) 2017-07-12 2019-01-16 Defymed Poche non pliable pour former un organe artificiel implantable
WO2019011939A1 (fr) 2017-07-12 2019-01-17 Defymed Poche non pliable pour former un organe artificiel implantable

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