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  • Us 20140093932 A 1

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    ingeniomeca8800
    15 vues32 pages
    Maquina de bioimpresion

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    Us 20140093932 a 1

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    15 vues32 pages

    Us 20140093932 A 1

    Transféré par

    ingeniomeca8800
    Maquina de bioimpresion

    Droits d'auteur :

    © All Rights Reserved
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    cu») United States v2) Patent Application Publication Murphy et al. (54) DEVICES, SYSTEMS, AND METHODS FOR THE FABRICATION OF TISSUE UTILIZING LINKING oy NOVO, INC., San Diego, CA (72) Inveators:Keith Murphy; Los Angeles, CA (US); Scott Dorfman, San Diego. CA (US) Richard Jin Law, Newbury Park, CA (US); Vivian Anne Le, San Diego, CA (ws) (93). Assignee: ORGANOVO, INC.,San Diego, CA ws QL) Appl. Nos 137794268 (22) Filed: Mar. 14,2013, Related US. Application Data Provisional application No, 61/636,442, filed on Apr 20, 2012. (60 (00 Pub. No: US 2014/0093932 Al (4s) Pub, Date: ‘Apr. 3, 2014 ‘US 20140093932, Publication Classification (1) Insel CRM x00 200601) CRM 10 (2005.01) CRN 500 (2006.01), (2) Us crc €12M 21/08 (2013.01); C12N S082 (2013.01); C12M 31/00 201301), usec 4RS/L7RA4; 435/286.3: 435/177 on ABSTRACT Described herein are bioprinters comprising: one or more printer beads, wherein a printer head comprises a means for receiving and bolding atleast one caridge, and wheceia said cartridge comprises contents selected from one of more of bio-ink, and support material: a UV Hight module for option: ally exposing the contents of atleast one cartridge to UV Tight; a means for calibrating the postion of atleast one cartridge; and a means for dispensing the contents of at least ‘one cartridge. Also described hi methods of sing-and bioprinting cartridges for such bioprinters AGAROSE BODY HASMC-HAEC BODY HDF BODY Patent Application Publication Apr. 3, 2014. Sheet 1 of 8 US 2014/0093932 AI CAPILLARY + t SENSOR THRESHOLD = MAX SENSING DISTANCE FIG. 1 Apr. 3, 2014 Sheet 2 of 8 ‘US 2014/0093932 AL Patent Application Publication REFLECTED UGHT ~ \ LASER SENSOR FIG. 2 Patent Application Publication Apr. 3, 2014 Sheet 3 of 8 US 2014/0093932 AI FIG. 3 Patent Application Publication Apr. 3, 2014 Sheet 4 of 8 US 2014/0093932 AI AGAROSE HASMC-HAEC HOF BODY BODY BODY FIG. 4 Patent Application Publication Apr. 3, 2014. Sheet 5 of 8 US 2014/0093932 AI FIG. 6 Patent Application Publication CAPILLARY ——8 UV CROSSLINKABLE HYDROGEL, Apr. 3, 2014 Sheet 6 of 8 US 2014/0093932 AI 365 nm AAA, ASDA 5 AVA AV AVA AU MISSI M™WDDAALIV Ja UV LAMP Apr. 3, 2014 Sheet 7 of 8 US 2014/0093932 AI Patent Application Publication ae a 816 820 FIG. 8 Apr. 3, 2014 Sheet 8 of 8 US 2014/0093932 AI Patent Application Publication he | Ma FIG. 9 US 2014/0093932 AI DEVICES, SYSTEMS, AND METHODS FOR ‘THE FABRICATION OF TISSUE UTILIZING UV CROSS-LINKING (CROSS-REPERENCE TO RELATED "APPLICATIONS, [0001] This application clims the benefit of US. Appl tion Ser. No. 61/636, 442 filed Apr 20, 2012, which is hereby Incomporated by reference in it entirety BACKGROUND OF INVENTION [0002] _ A numberof pressing problems confront the health- ‘care indusiry. As of December 2009 there were 105,305 patients registered by United Network for Organ Sharing (UNOS) as needing an organ tansplant. Between January and September 2009, only 21,423 transplants were per- ormed. Fach year more patients are added to the UNOS Tist than ransplans are performed, resulting in a net increase in the number of patents waiting for transplant, For example, atthe beginning of 2008, 75.834 people were reyistered as needing a kidney; atthe end of that year, the number had ‘grown to 80,972. 16,546 kidney transplants were performed, that yea, but 33,005 nev patients were added to the list. The 2008 transplant rate for & patient registered by UNOS as needing & kidney was 20%. The mortality rate of wailist patients was 7%. 10003) Additionally, the rescarchand development costofa new pharmaceutical compound sapproximately $1 illion. See Paul tal (2010). How to improve R&D productivity the pharmaceutical industry’s grand challenge. Nature Reviews Drug Discovery 9(3}:203-214. Drag discovery isthe process by which drugs are discovered and/or designed. The process of drug discovery generally involvesat less the steps ‘of, identification of candidates, synthesis, characterization, sereening, and assays for thenpeutie eficacy. Despite advances in technology and understanding of biological sys. tems, drug discover is still a longthy, expensive, and inft- ‘cient paces with low rate of new thenspeutie discovery. SUMMARY OP THE INVENTION 10004) ‘There is » need for tools and techniques that fac (copplication of regenerative medicine and issue engineer ing technologies to rlioving the urgent need for tissues and ‘organs. There is also a need for tools and techniques that substantially increase the number and quality of innovative, ‘costfective new medicines, without incurring ussusain= able RAD casts. Accordingly the inventors describe herein devices, systems, axl methods for fabricating tissues and ‘organs. [0005] -Inone aspect, disclosed herein are bioprinters com prising: one or more printer heads, wherein a peter head ‘comprises a means for receiving and hokfing atleast one ‘cartridge, and wherein said cartridge comprises contents selected from one or more of bio-ink and support material: 2 UY light module for opGonaly exposing the conteats of at Jeast one cartridge to UV light; ands means for dispensing the ‘contents of at least one cartridge. In some embodiments, the mans for dispensing the contents of atleast one cartridge is application of a piston, application of pressure, applieation of ‘compressed gas, hydmilies, or a combination thereof. In some embodiments, the bio-ink oF support material con- Prises one or more UV cross-linkable materials. In some ubowiments, the UV light module exposes the conteats ofa Apr. 3, 2014 least one cartridge to UV Tight prior to dispensing, In some ‘embodiments, the UV light module is tunable with respect wavelength, intensity, exposure time, or any combinstion thereof In furher embodiments, the UV light module com- prises one or more optionally engaged attention filters, ‘wherein the attenuation filters lower UV intensity when ‘engaged, In some embostiments, the bioprintr further com prises a means for applying a wetting agent to one or more of printer stage; a receiving surface; a Ueposition orifice; the bio-ink: the support materials and a. printed constrict ‘wherein the setting agent is applied st one or more time points selected from: before the bio-ink or suppor material is isponsed by the bioprinter, substantially concurrently with ‘Gspensing, and aller the biocink or support material is pense by the bioprinter, [0006] In another aspect, disclosed herein are methods of fabricating a tissue consiict comprising the steps of depos iting bio-ink onto a support, wherein the bio-ink comprises a LUV eross-linkable material and as boen expose to UV light {o partially or completely crosslink the UV cross-linkable ‘material to form a semi-solid or solid body; and incubating the bio-ink to allow it to cohere and to forma tissue, where sad incubation has a doration of about 1 hour to about days. Ia some embodiments, the method further comprises the step of preparing aliquid bio-ink soktion eomprising a UV cross-linkable material and cells. In further embodi- ‘mens, the method further comprises the step of exposing a liquid bo-ink solution comprising a UV cross-linkable mate- ial and cells to UV light to partially or completely cros-link the UV crosslinkable material to form a semi-solid oF soi body. In some embodiments, the method furher comprises the step of depositing bio-ink onto a support, wherein the bio-ik comprises a UV erost-linkble material ad has not been exposed to UV light. In some embodiments, the UV cross-linkable material is @ hydrogel. In some embodiments, the biosink comprises mammalian cells. In futher embed reals, the bio-ink comprises differentiated, mammalian cells. In forther embodiments, the biorink comprises non- dillerentated, mammalian cells. In some embodiments, the bio-ink is deposited by extrusion Irom a bioprinter. [0007] In another aspect, disclosed herein ae bioprinter ‘arteidges, wherein the eontents of the cartridge comprises a [DV crosslinkable material and optionally eels. In some embodiments, the UV cross-linkable material is partially or completely cross-linked. In some embodiments, the UV ‘ros-linkable material is a hydrogel. In some embodiments, the cartridge comprises a glass-walled reservoir. In some ‘embodiments, the cartridge is permeable to UV light [0008] In another aspect, disclosed Nerein are UY light ‘modules fora bioprinter comprising a UV light source that ‘optionally exposes the contents of at least one biopriner cartridge to UV light. In some embodiments, the UV light ‘edule is reversibly atachable to a bioprinter. In some ‘embodiments, the UV light module is tunable with respect t0 ‘wavelength, intensity, exposure time, or any combination thereof. In some embodiments, the UV Tight module furher comprises one or moreptionally engaged attenuation filters, Wherein the attenuation filters lower UV intensity when engaged. [0009] tn another aspect, diselosed herein ae tissue con- structs comprising multicellular body on a support sub- strate, wherein the multicellular body comprises a UV eross- Tinkable material and cells, where the multicelar body vas deposited by a bioprnter, provided thatthe muleellular US 2014/0093932 AI body was exposed to UV light to partially of con ‘eross-link the UV cross-linkable material to form a semi solior sold body. In some embuxliments, the construct com- prises « plurality of multicellular bodies. In some embodi- ments, the UV cross-linkable material sa hydrogel. In some ‘embodiments, the multicellular body comprises different ‘ated, mammalian cells. In some embodiments, the multicel- Iular body comprises non-differentinted, mammalian cells BRIEF DESCRIPTION OF FIGURES [0010] FIG. 1 illustrates a non-limiting example of calibra- thon ofa caridgeusinga hernias [0011] 11G.2sIhsintesa nonlimiting example calibra Som ofa carpe sing a vertal laser [0012] FIG. 3ilhnrtes s nonsiniting example of «cape ‘lary pining process. [0013] FIG. 4 illustrates a non-limiting example of a two- ‘iensional representation ofa bio-prined tase consti [0014 FIG. Sisters noelimting example ofa three- lmensional costae genestd by continuous deposition of PI-T37 ising Novoen MMX™ biopinter connected to syringe wth 510m aed in his cave, pyramidsbaned [0015]. FIG. 6ithusttes nonlimiting example ofa tree- Slimensional costuc generated by continuous deposition of Pict37 sings Novoen MMX™ bioprnter connected syringe with a 510 um needle; in this case, cube-shaped (left) sd hollow cube-sbaped (ight) comnts [0016] 116.7 iostates a no-limiing schematic ogra depicting exemplary parameters for exposing a UV cross- linkable mera fo UV light source inthe context of Sionsnter [0017] FIG. 8 illustrates a non-limiting example of a Novo- Geo MMX"™ bopiterinchatinga UV mode in tinea, ‘printer ead is positioned such tat a capillary abe par tal incuced toa UV module [0018] FIG. 9 illustrates a non-limiting example of a Novo- Gen MMX'™ boprinterincludings UN mod inthiscase, 4 printer head is positioned sch that capillary tbe is ‘alizlyinteduced oa UV module DETAILED DESCRIPTION OF INVENTION 10019] The invention relates to the fields of regenerative medicine, tisuelorgan engineering. biologie and medical research, and drug discovery. More particularly, the invention relates to devices for fabricating tissues and ongans, systems and methods for calibrating and using such devices, and ts- sues and organs fibricated by the devices, systems, and meth- ‘ods disclosed herein 10020] Disclosed herein, in certain embodiments, are bio- printers comprising: one or more prater heads, wherein & Printer head comprises a means for receiving and holding st Teast one carridge, and wherein said cartridge comprises ‘conten selected from one or more of: bio-ink and support material; a UV light mele for optionally exposing the con- tents of atleast one cartridge to UV light: and a means for

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