EP1139915A1 - Appareil et procede pour steriliser, ensemencer, mettre en culture, stocker, expedier ou tester des greffons vasculaires tissulaires, synthetiques ou naturelles - Google Patents

Appareil et procede pour steriliser, ensemencer, mettre en culture, stocker, expedier ou tester des greffons vasculaires tissulaires, synthetiques ou naturelles

Info

Publication number
EP1139915A1
EP1139915A1 EP00909911A EP00909911A EP1139915A1 EP 1139915 A1 EP1139915 A1 EP 1139915A1 EP 00909911 A EP00909911 A EP 00909911A EP 00909911 A EP00909911 A EP 00909911A EP 1139915 A1 EP1139915 A1 EP 1139915A1
Authority
EP
European Patent Office
Prior art keywords
graft
chamber
fluid
vascular
vascular graft
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Withdrawn
Application number
EP00909911A
Other languages
German (de)
English (en)
Inventor
Michael R. Fino, Jr.
Ann A. Lee
Mark F. Baumgartner
Fred R. Koller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Advanced Tissue Sciences Inc
Original Assignee
Advanced Tissue Sciences Inc
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 Advanced Tissue Sciences Inc filed Critical Advanced Tissue Sciences Inc
Publication of EP1139915A1 publication Critical patent/EP1139915A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A61F2/062—Apparatus for the production of blood vessels made from natural tissue or with layers of living cells

Definitions

  • the present invention relates to the sterilization, seeding, culturing, storing, shipping, and testing of vascular grafts and other prosthetic devices. Specifically, the present invention relates to an apparatus and method for sterilizing vascular grafts and then seeding and culturing the grafts with human cells, resulting in grafts that are more likely to display the biochemical, physical, and structural properties of native tissues.
  • vascular grafts to repair or replace segments of arterial and venous blood vessels that are weakened, damaged, or obstructed due to trauma or disease, such as aneurysm, atherosclerosis, and diabetes mellitus.
  • vascular grafts have been either homografts, such as the patient's own saphenous vein or internal mammary artery, prosthetic grafts made of synthetic materials such as polyester (e.g. , Dacron), expanded polytetraflouroethylene (ePTFE), and other composite materials, or fresh or fixed biological tissue grafts.
  • tissue engineered grafts Due to the inadequacies of these currently available synthetic and biological grafts, and the high cost and limited supply of homografts, tissue engineered grafts are being developed which are sterilized, then seeded and cultured, in vitro, with cells. These tissue engineered grafts may be superior to other grafts for use in replacement therapy in that they may display the long term dimensional stability and patency of native arteries and vessels with normal physiologic functionality.
  • the apparatus comprises a fluid reservoir, a pump, at least one graft treatment chamber (treatment chamber), and an alternating pressure source.
  • the apparatus includes a means for attaching at least one vascular graft directly in-line with the fluid reservoir. The pump forces fluid through the vascular graft, thereby subjecting it to radial and shear stresses.
  • the alternating pressure source expands and contracts the treatment chamber, thus applying axial stress to the vascular graft secured within the treatment chamber during seeding and culturing. Applying shear, radial, and axial stresses to the vascular graft in this fashion during seeding and culturing simulates physiological conditions. This is believed to produce a prosthesis that is more likely to tolerate the physiological conditions found in the human body once implanted.
  • the apparatus comprises a fluid reservoir, a pump, a cartilage treatment chamber, and an alternating pressure source.
  • the pump forces fluid around and through the cartilage graft, while the alternating pressure source expands and contracts the treatment chamber, thereby applying alternating pressure to the cartilage graft secured within the treatment chamber during seeding and culturing.
  • the invention advantageously utilizes a mechanically non-complex apparatus to create a dynamic environment in which to seed and culture tissue engineered vascular grafts or other implantable devices.
  • FIG. 1 is a schematic diagram illustrating an apparatus according to the present invention for sterilizing, seeding, culturing, storing, shipping, and testing a prosthesis;
  • FIG. 2 illustrates a vascular graft treatment chamber containing a vascular graft
  • FIG. 3 illustrates a cartilage treatment chamber containing a cartilage graft.
  • FIG. 1 discloses a system for sterilizing, seeding, culturing, storing, shipping, and testing a prosthesis.
  • this system primarily comprises a fluid reservoir 110, a pump 112, a treatment chamber 114, and an alternating pressure source 116.
  • Fluid reservoir 110 is used to store fluid for the system.
  • Illustrative suitable reservoirs include a Gibco-BRL 1L media bag and any other rigid container capable of sterilization.
  • Reservoir 110 may include a bacterial-retentive filter 111 so as to provide a direct source of gas to the fluid within the system.
  • fluid which may be used in the system include, but are not limited to, sterilizing fluid, tanning fluid, fluid containing cells, or fluid containing a culture medium. It is to be understood that during testing, seeding, and culturing in a preferred embodiment, the fluid may be advantageously kept at human body temperature, and may be composed of a fluid which approximates the viscosity of human blood.
  • a solution which approximates the viscosity of blood is saline with glycerol.
  • Fluid line 118 may be made of any type of medical grade, durable tubing — such as silicone tubing — which is suitable for transporting the fluid in use.
  • Pump 112 may be any fluid pump which can achieve variable flow rates. One such pump is the Masterflex L/S Digital Drive peristaltic pump manufactured by Cole-Palmer, although one skilled in the art could select from a variety of commercially available pumps. Pump 112 propels the fluid from reservoir 110 to treatment chamber 114 through fluid line 120.
  • a pulse dampener 119 may be used along fluid line 120, between pump 112 and treatment chamber 114, to dampen the pulsatility of the fluid flow from pump 112. Suitable dampeners include the Masterflex airspring dampeners available from Cole-Palmer.
  • a timed valve 123 may also be utilized, in conjunction with a pressure control valve 148, to provide an alternating fluid pressure to treatment chamber 114.
  • pressure control valve 148 can be configured to create a desired pressure along fluid line 120. Once timed valve 123 is opened, this pressure is released through treatment chamber 114.
  • a controllable and repeatable pulsatile fluid flow may be provided to treatment chamber 114. This pulsatile flow in turn places a varying radial stress on vascular graft 126 (shown in FIG. 2) housed within treatment chamber 114, thereby producing a vascular graft that is more likely to tolerate the physiological conditions found in the human body once implanted.
  • this pulsatile flow is created using timed valve 123, those of skill in the art will appreciate that there are other well-known means (including for example using the peristaltic pump without a flow dampener) for providing a pulsatile fluid flow to chamber 114.
  • a pressure transducer 140 and flow transducer 141 may also be placed in fluid line 120 between pump 112 and treatment chamber 114 to measure the pressure and flow of fluid into treatment chamber 114.
  • Suitable pressure tranducers are the Transpac IV flow- through pressure gauge sold by Abbott Critical Care Systems, and the Honeywell flow- through pressure gauge sold by Newark Electronics. Signals from these transducers may be provided to a supervisory control and data acquisition system 149, which in one preferred embodiment, is the Lab VIEW control and data acquisition system sold by National Instruments. As is discussed herein, system 149 is used to provide appropriate electronic signals to create, and then monitor, the physiological conditions in the system of FIG. 1 that are beneficial to the particular tissue being seeded and cultured.
  • treatment chamber 114 comprises a main body 150 (made of, for example, cylindrical polycarbonate tubing), a top end cap 152, and a bottom end cap 154.
  • Main body 150 is secured to cap 152 through any standard, leak-proof means, such as inner and outer threads or bonding agents.
  • Main body 150 is secured to bottom cap 154 by a bellows 156, which provides a flexible joint in treatment chamber 114 along its vertical axis.
  • Bellows 156 comprises any suitable elastomeric material, such as polyurethane or silicone, and may be dip molded. Bellows 156 is attached to body 150 and cap 154 by any suitable means, such as a band clamp.
  • Treatment chamber 114 additionally comprises a bottom mandrel 128 and a top mandrel 133.
  • bottom mandrel 128 is inserted into treatment chamber 114 through the top of the chamber, and is then secured to bottom cap 150 through any appropriate means, such as the inner and outer threads shown in FIG. 2.
  • the connection between cap 150 and mandrel 128 may be made leak proof through use of a silicone o-ring 155.
  • tubing 120 is inserted through the bore of mandrel 128 into treatment chamber 114, where it is securely attached to the vascular graft 126 by an adapter port 158.
  • Adapter port 158 is firmly attached to mandrel 128 using, for example, inner and outer threads.
  • adapter port 158 includes only one port in FIG. 2, a person of ordinary skill in the art will recognize that adapter ports 158 may be branched so that multiple ends of a branched (e.g., y-shaped) vascular graft may be attached to adapter ports 158 in the manner described herein. Therefore, particular embodiments of the instant invention enable one skilled in the art to seed, culture, or treat single branch or multibranched vascular grafts.
  • Adapter port 158 is secured to vascular graft 126 by any conventional means, such as sutures, c-clips, surgical staples, medical grade bonding agents, tie wraps, or elastomeric bands.
  • vascular graft 126 can be placed within a larger diameter port 158 and secured by compressing vascular graft 126 against port 158.
  • Adapter port 158 may be comprised of a slightly porous material to allow for tissue ingrowth at the attachment sites.
  • Top cap 152, top mandrel 133, top port 158, and fluid line 122 are all attached in the same fashion as has been described in conjunction with the lower half of treatment chamber 114, once lower mandrel 128 is secured to treatment chamber 114.
  • a viewing port may 5 be placed at any point on the chamber, or alternatively, the chamber may be made of an optically clear material such as polycarbonate or PVC.
  • the components of treatment chamber 114 may be composed of any biocompatible, rigid material capable of being sterilized such as Teflon, PVC, or stainless steel. Moreover, it can also be made of
  • fluid may be passed through treatment chamber 114 beginning at bottom mandrel 128. More specifically, fluid enters mandrel 128 from fluid line 120 and then passes through vascular graft 126 to upper
  • fluid line 125 connects mandrel 133 to inlet port 131, which allows the fluid to re-enter treatment chamber 114, and perfuse across the exterior surface of vascular graft 126. Once fluid has perfused across graft 126, it re-exits
  • Outlet port 130 is secured to fluid line 122.
  • valve 129 is closed, for example, during seeding of graft 126.
  • fluid is forced to enter vascular graft 126, perfuse through graft 126 due to back pressure, and then exit chamber 114 through port
  • valve 129 Utilizing valve 129 in this fashion ensures that graft 126 is appropriately seeded during the initial stages of treatment by forcing cells through graft 126. Once the appropriate level of seeding has been reached, valve 129 can be opened so that fluid flow proceeds in accordance with the above description.
  • Fluid passing through, and across, vascular graft 126 may cause the vascular graft to undulate.
  • a support member such as a skeletally-configured rod, may be attached by any conventional means to the adapter ports 158 to suppress such undulations.
  • the vertical orientation of the grafts shown in FIG. 2 is not necessary if the graft is supported by such an internal support structure which does not unduly obstruct flow across the interior surfaces of the grafts which create shear stresses.
  • Such support structures could additionally include a splint structure or rigid tubular screens with large, unobstructing openings.
  • pressure source 116 comprises a pneumatic cylinder 170, a four-way solenoid valve 172, a flow control valve 174, a bottom position sensor 176, and a top position sensor 178.
  • air is provided to pressure source 116 from air supply 180. The air pressure is controlled by flow control valve 174, which is connected to four- way solenoid valve 172.
  • Solenoid valve 172 is actuated by control system 149 in a fashion which creates a desired strain profile on the tissue to be seeded and cultured. More specifically, by actuating valve 172 using control system 149, the piston in pneumatic cylinder 170 is alternately driven between its top and bottom positions. Control system 149 receives electrical indications that these positions have been reached, respectively, by top position sensor 178 and bottom position sensor 176. By alternately elongating and then contracting chamber 114, a varying axial stress is advantageously placed on graft 126. This axial stress is advantageous as it simulates in-vivo conditions, resulting in three dimensional tissue that is more likely to display the biochemical, physical, and structural properties of native tissue.
  • alternating pressure source 116 may be attached to either the top of bottom of treatment chamber 114 (which are separated by bellows 156) by any suitable means.
  • alternating pressure source 116 should be secured in place so as to remain in a fixed position during treatment.
  • any means for applying alternating pressure to chamber 114 along its vertical axis may be utilized. Such means would include, for example, a rotary motor driving an appropriate cam configuration.
  • treatment chamber 114 houses vascular graft scaffolding 126.
  • graft 126 may illustratively consist of any knitted, braided, woven, felted, or synthesized materials that are bioresorbable and/or biocompatible, as well as any native graft scaffolding material.
  • Treatment Chamber 114 may be made any length or diameter so as to hold a vascular graft scaffolding 126 of any length or diameter. This is advantageous, as the system may be used to sterilize, seed, culture, store, ship, and test vascular grafts of any size, such as coronary, carotid, iliac, and peripheral leg grafts.
  • a treatment chamber 214 similar to treatment 114, may be devised to seed, culture and treat a cartilage graft 226 in conjunction with the system of FIG. 1.
  • Chamber 214 is identical in many respects to chamber 114.
  • chamber 214 includes only a single inlet 230 and a single outlet 231.
  • Upper mandrel 200 and lower mandrel 202 are solid structures, and include no bore.
  • fluid flows into inlet port 230 and then flows around the exterior of a nonporous plate 204, which is attached to upper adapter port 158. Fluid then perfuses through and across graft 226, through porous plate 206, and finally, through outlet port 231. While fluid is perfusing through and across graft 226 in this fashion, alternating pressure source 116 is used to alternatively expand and contract chamber 214. This expansion and contraction causes the volume between plates 204 and 206 to alternately compress and expand, thus placing a varying pressure on substrate 226.
  • plate 204 is a porous plate similar to porous plate 206.
  • fluid entering chamber 214 through port 230 passes through plate 204.
  • Graft 226 may attach to plate 204 or 206 as shown, or graft 226 may be mounted in a support structure (not shown) between plates 204 and 206.
  • fluid enters and exits chamber 214 through both ports 230 and 231.
  • alternating pressure source 116 is used to alternatively expand and contract chamber 214 as described above.
  • Expansion and contraction of chamber 214 causes the volume between plates 204 and 206 to alternately compress and expand, thus placing a varying pressure (contact pressure and/or fluid pressure) on substrate 226.
  • the substrate 226 may be alternatingly relaxed and compressed between 0% strain and 75 % during the early stages of growth, and between 25% and 75% during the later stages.
  • magnitude, frequency and duration of compression and relaxation of substrate 226 may be selected and varied to optimize culture conditions and/or to simulate in vivo conditions.
  • the system of FIG. 1 contains a plurality of chambers 114 for treating a plurality of vascular grafts 126.
  • fluid line 120 may be split to connect to as many additional chamber inlets 121 as is desired, and fluid line 122 may be split to connect to as many additional chamber outlets 144 as is desired.
  • multiple pressure sources 116 may be utilized, one skilled in the art will appreciate that a single pressure source may be connected in parallel with multiple treatment chambers 114.
  • each treatment chamber 114 may be connected to a separate reservoir 110 and pump 112 so that multiple treatment chambers in a system would only share a single alternating pressure source 116.
  • pump 112 with multiple pump lines may also be used so that each treatment chamber 114 in the system would use the same alternating pressure source and same pump 112 (each using a different pump line), but would be connected to a different fluid reservoir 110. In this manner, a plurality of vascular grafts may be simultaneously seeded, cultured, or tested in accordance with the present invention.
  • the system disclosed in FIG. 1 may additionally include a pressure transducer 142 and flow transducer 143 at the outlet of treatment chamber 114. These transducers can provide additional data to control and data acquisition system 149, so that said system can ensure desirable strain profiles on the tissue to be cultured.
  • a flow control valve 146 can be placed along fluid line 122, so that an ambient pressure within treatment chamber 114 that is greater than atmospheric pressure can be maintained if desired.
  • a pH indicator 161 and an oxygen content indicator 160 may be fluidly connected to reservoir 110, so as to periodically measure the pH level and oxygen content of the fluid in the system.
  • the inlet ports and outlet ports of treatment chamber 114 may be sealed in a known manner (e.g., luer locks or threaded plugs) so as to create a sealed treatment chamber free from contamination.
  • the sealed chambers may be used to sterilize, store, and ship vascular grafts or other protheses.
  • vascular graft scaffolding 126 which is secured within sealed chamber 114 may be sterilized by some chemical means such as ethylene oxide or peracetic acid, radiation means such as an electron beam or gamma rays, or by steam sterilization.
  • Sealed treatment chamber 114 containing the sterilized vascular graft scaffolding, or the sterilized vascular graft may then be placed back into the system FIG. 1 for seeding and culturing and unsealed without contaminating the system or the vascular graft.
  • Seeding and culturing of the vascular graft in treatment chamber 114 is generally accomplished by known techniques, with the added benefits and advantages gained from the radial, shear, and axial stresses placed upon the vascular graft during growth.
  • suitable seeding and culturing methods for the growth of three-dimensional cell cultures are disclosed in U.S. Patent No. 5,266,480 and in U.S. patent application serial no. 08/487,749, which was filed June 7, 1995 and is entitled "In Vitro Preparation of Tubular Tissue Structures by Stromal Cell Culture on a Three Dimensional Framework", both of which are incorporated herein by reference.
  • 08/487,749 for establishing a three-dimensional matrix, inoculating the matrix with the desired cells, and maintaining the culture may also be readily adapted by a person of ordinary skill in the art for use with the present invention.
  • a preservative may then be pumped into treatment chamber 114.
  • the inlet ports and outlet ports of the chamber may be closed, again creating a sealed chamber which may then be used to store and/or ship the cultured and preserved vascular graft.
  • the preservative is a cryo-preservative so that the graft may be frozen in chamber 114. In this manner, sealed treatment chamber 114 may be used to sterilize, culture, store, and ship vascular grafts or other protheses.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Materials For Medical Uses (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Appareil et procédé pour stériliser, ensemencer, mettre en culture, stocker, expédier ou tester des greffons vasculaires et autres prothèses. L'invention concerne en particulier un appareil et un procédé pour ensemencer et mettre en culture des greffons vasculaires avec des cellules humaines. L'appareil comprend un réservoir à fluide, une pompe, une source de pression alternative, et au moins une chambre de traitement. Selon l'invention, le fluide est pompé directement à travers le greffon vasculaire disposé à l'intérieur de la chambre de traitement, et soumet le greffon vasculaire à des contraintes radiales et de cisaillement. En outre, la source de pression alternative gonfle et contracte la chambre de traitement, exerçant ainsi une contrainte axiale variable sur le squelette placé à l'intérieur de la chambre de traitement. L'application de contraintes de cisaillement, radiales, et axiales sur le greffon vasculaire au cours de l'ensemencement et de la mise en culture stimule les états physiologiques marquant le greffon après son implantation.
EP00909911A 1999-01-14 2000-01-14 Appareil et procede pour steriliser, ensemencer, mettre en culture, stocker, expedier ou tester des greffons vasculaires tissulaires, synthetiques ou naturelles Withdrawn EP1139915A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US11865699P 1999-01-14 1999-01-14
US118656P 1999-01-14
PCT/US2000/001003 WO2000041648A1 (fr) 1999-01-14 2000-01-14 Appareil et procede pour steriliser, ensemencer, mettre en culture, stocker, expedier ou tester des greffons vasculaires tissulaires, synthetiques ou naturelles

Publications (1)

Publication Number Publication Date
EP1139915A1 true EP1139915A1 (fr) 2001-10-10

Family

ID=22379948

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00909911A Withdrawn EP1139915A1 (fr) 1999-01-14 2000-01-14 Appareil et procede pour steriliser, ensemencer, mettre en culture, stocker, expedier ou tester des greffons vasculaires tissulaires, synthetiques ou naturelles

Country Status (6)

Country Link
EP (1) EP1139915A1 (fr)
JP (1) JP2002534210A (fr)
AU (1) AU3209400A (fr)
CA (1) CA2359589A1 (fr)
IL (1) IL144187A0 (fr)
WO (1) WO2000041648A1 (fr)

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US6632651B1 (en) * 1999-07-06 2003-10-14 Ramot At Tel Aviv University Ltd. Tissue maintenance system that applies rhythmic pulses of pressure
US9522217B2 (en) 2000-03-15 2016-12-20 Orbusneich Medical, Inc. Medical device with coating for capturing genetically-altered cells and methods for using same
JP4230176B2 (ja) * 2002-06-28 2009-02-25 独立行政法人科学技術振興機構 胚の培養装置及び胚の左右非対称性を制御する方法
GB0229274D0 (en) * 2002-12-16 2003-01-22 Anson Medical Ltd Instrument for testing pulsatile endurance of vascular implants
US7794408B2 (en) 2003-03-28 2010-09-14 Ethicon, Inc. Tissue collection device and methods
US8034003B2 (en) 2003-09-11 2011-10-11 Depuy Mitek, Inc. Tissue extraction and collection device
EP2946666B1 (fr) 2004-04-30 2017-11-15 OrbusNeich Medical, Inc. Dispositif médical avec revêtement permettant de capturer des cellules génétiquement modifiées et procédés d'utilisation de celui-ci
EP1788974A1 (fr) * 2004-09-16 2007-05-30 The National University of Ireland, Galway Procede servant a evaluer un materiau biologique et bioreacteur associe
WO2008017128A1 (fr) * 2006-08-11 2008-02-14 The University Of Queensland Dispositif et procédé de traitement de supportsMATRICES
US7624648B2 (en) * 2007-06-26 2009-12-01 Bose Corporation System and method for multi-axes simulation
US7587949B2 (en) 2007-07-20 2009-09-15 Bose Corporation System and method for stimulation and characterization of biologic materials
JP5148397B2 (ja) * 2008-07-18 2013-02-20 株式会社クラレ 細胞培養容器および細胞培養方法
KR101435402B1 (ko) 2010-05-17 2014-08-28 예일 유니버시티 3 차원 스캐폴드 상에 세포 접종을 위한 시스템
US9090863B2 (en) 2010-05-17 2015-07-28 Pall Corporation System for seeding cells onto three dimensional scaffolds
JP5769334B2 (ja) 2011-02-04 2015-08-26 国立大学法人佐賀大学 移植用ガイドおよび移植用器具
EP3488386A4 (fr) * 2016-07-22 2020-02-19 Cornell University Prototypage rapide et modélisation in vitro de greffes de pontage aorto-coronarien spécifiques à un patient

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Also Published As

Publication number Publication date
WO2000041648A1 (fr) 2000-07-20
CA2359589A1 (fr) 2000-07-20
JP2002534210A (ja) 2002-10-15
AU3209400A (en) 2000-08-01
IL144187A0 (en) 2002-05-23

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