Granted Patent
B2
US 12,642,890 · App. 18/107,308 · Granted Jun 2, 2026
Biomaterials for enhanced implant-host integration
Inventors:
Christopher S. Chen (Newton, MA); Jan D. Baranski (Philadelphia, PA); Ritika Chaturvedi (Philadelphia, PA); Michael T. Yang (West Windsor, NJ); Kelly Stevens (Seattle, WA); Sangeeta Bhatia (Lexington, MA)
A61L27/50A61K35/44A61L27/225A61L27/24A61L27/3604A61L27/3804A61L27/3808A61L27/3834A61L27/3839A61L27/3886A61L27/40A61L27/507A61L2430/20A61L2430/28
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Abstract
The present disclosure provides patterned biomaterials having organized cords and extracellular matrix embedded in a 3D scaffold. According, the present disclosure provides compositions and applications for patterned biomaterials. Pre-patterning of these biomaterials can lead to enhanced integration of these materials into host organisms, providing a strategy for enhancing the viability of engineered tissues by promoting vascularization.
Claims (13)
1 . A method of enhancing the survival and/or function of hepatocytes following implantation, comprising:
(1) providing a patterned biomaterial comprising:
(a) at least one cord, formed by embedding cells in a naturally-derived or synthetic scaffolding with a pre-specified architecture and spatially organizing the cells within the scaffolding, wherein the cells embedded in the naturally-derived or synthetic scaffolding consists of endothelial cells; and
(b) at least one cluster of hepatocytes; and
(2) implanting the patterned biomaterial into a tissue of the subject, wherein the patterned biomaterial is configured to promote the vascularization of the patterned biomaterial and the tissue of the subject, wherein the structure of the patterned biomaterial has a pre-specified architecture that acts as a template and spatial guidance for the subject's vasculature, thereby enhancing the survival and/or function of the hepatocytes following implantation.
2 . The method of claim 1 , wherein the patterned biomaterial further comprises an extracellular matrix or other physically solid scaffold at least partially encapsulating the at least one cord.
3 . The method of claim 2 , wherein the extracellular matrix comprises fibrin.
4 . The method of claim 1 , wherein the at least one cord is branched.
5 . The method of claim 1 , wherein the at least one cord comprises a plurality of cords.
6 . The method of claim 5 , wherein the plurality of cords is formed in a parallel arrangement within the naturally-derived or synthetic scaffolding.
7 . The method of claim 5 , wherein the plurality of cords is formed in a nonparallel arrangement within the naturally-derived or synthetic scaffolding.
8 . The method of claim 1 , wherein the at least one cord is cylindrical, Y-shaped, or T-shaped.
9 . The method of claim 1 , wherein the at least one cord is solid or hollow in cross-section.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 2, 2023
From: STEVENS, KELLY; BHATIA, SANGEETA
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 063839/0869 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 2, 2023
From: CHEN, CHRISTOPHER S.; BARANSKI, JAN D.; CHATURVEDI, RITIKA; YANG, MICHAEL T.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 063840/0031 →
Continuity (5)
Continuation
PCTUS2013049933
· Jul 10, 2013
Provisional Application
61670100
· Jul 10, 2012
References Cited (245)
US 4853332A
· Mark et al.
· 1989
[cited by applicant]
US 5116964A
· Capon et al.
· 1992
[cited by applicant]
US 5123950A
· Homma et al.
· 1992
[cited by applicant]
US 5624840A
· Naughton et al.
· 1997
[cited by applicant]
US 5712161A
· Koezuka et al.
· 1998
[cited by applicant]
US 6368612B1
· Lanza et al.
· 2002
[cited by applicant]
US 6509514B1
· Kneteman et al.
· 2003
[cited by applicant]
US 6864402B1
· Rogler et al.
· 2005
[cited by applicant]
US 6995299B2
· Wu et al.
· 2006
[cited by applicant]
US 7273963B2
· Kneteman et al.
· 2007
[cited by applicant]
US 7498479B2
· Kneteman et al.
· 2009
[cited by applicant]
US 7626075B2
· Beschorner et al.
· 2009
[cited by applicant]
US 8852932B2
· Forgacs et al.
· 2014
[cited by applicant]
US 20020182633A1
· Chen et al.
· 2002
[cited by applicant]
US 20040126405A1
· Sahatjian et al.
· 2004
[cited by applicant]
US 20050053642A1
· Ulbricht et al.
· 2005
[cited by applicant]
US 20060258000A1
· Allen et al.
· 2006
[cited by applicant]
US 20060270032A1
· Bhatia et al.
· 2006
[cited by applicant]
US 20070275080A1
· Laulicht et al.
· 2007
[cited by applicant]
US 20080075750A1
· Akins
· 2008
[cited by applicant]
US 20080226604A9
· Kellar et al.
· 2008
[cited by applicant]
US 20080280360A1
· Kaplan et al.
· 2008
[cited by applicant]
US 20090035855A1
· Ying et al.
· 2009
[cited by applicant]
US 20090117655A1
· Kubota et al.
· 2009
[cited by applicant]
US 20090319033A1
· Niklason et al.
· 2009
[cited by applicant]
US 20100040584A1
· Melero-Martin
· 2010
[cited by examiner]
US 20100168872A1
· Brown et al.
· 2010
[cited by applicant]
US 20100184220A1
· Ram-Liebig et al.
· 2010
[cited by applicant]
US 20100189712A1
· L'Heureux et al.
· 2010
[cited by applicant]
US 20100278798A1
· Sia et al.
· 2010
[cited by applicant]
US 20100285094A1
· Gupta
· 2010
[cited by applicant]
US 20120141547A1
· Zhao et al.
· 2012
[cited by applicant]
US 20150087004A1
· Chen et al.
· 2015
[cited by applicant]
US 20190376024A1
· Bhatia et al.
· 2019
[cited by applicant]
US 20220354994A1
· Bhatia et al.
· 2022
[cited by applicant]
EP 1083945A1
· 2001
[cited by applicant]
EP 1500697A2
· 2005
[cited by applicant]
EP 1939280A1
· 2008
[cited by applicant]
WO WO199408570A1
· 1994
[cited by applicant]
WO WO199952573A1
· 1999
[cited by applicant]
WO WO2004046337A2
· 2004
[cited by applicant]
WO WO2006001778A1
· 2006
[cited by applicant]
WO WO2008148026A1
· 2008
[cited by applicant]
WO WO2012048170A3
· 2012
[cited by applicant]
WO WO2014011775A1
· 2014
[cited by applicant]
Zorlutuna et al., (Mar. 13, 2012) Microfabricated Biomaterials for Engineering 3D tissues. Advanced Biomaterials, 24(14):pp. 1782-1804. (Year: 2012).
[cited by examiner]
Raghavan et al., (Jul. 2010) Geometrically controlled endothelial tubulogenesis in micropatterned gels. Tissue Engineering Part A, 16(7): pp. 2255-2263 (Year: 2010).
[cited by examiner]
Abu-Absi et al., Structural polarity and functional bile canaliculi in rat hepatocyte spheroids. Exp Cell Res. Mar. 10, 2002;274(1):56-67.
[cited by applicant]
Aird, Endothelium in health and disease. Pharmacol Rep. Jan.-Feb. 2008;60(1):139-43.
[cited by applicant]
Akselrod et al., Laser-guided assembly of heterotypic three-dimensional living cell microarrays. Biophys J. Nov. 1, 2006;91(9):3465-73.
[cited by applicant]
Albrecht et al., Probing the role of multicellular organization in three-dimensional microenvironments. Nat Methods. May 2006;3(5):369-75.
[cited by applicant]
Antonchuk et al., AggreWell 400 and AggreWell 800 Provide a Unique Platform for Generation of Size-Controlled Aggregates Including Human Embryoid Bodies. STEMCell Technologies, Poster Presentation, 1 page, (2010).
[cited by applicant]
Arcaute et al., Stereolithography of three-dimensional bioactive poly(ethylene glycol) constructs with encapsulated cells. Ann Biomed Eng. Sep. 2006;34(9):1429-41.
[cited by applicant]
Atala, Engineering organs. Curr Opin Biotechnol. Oct. 2009;20(5):575-92.
[cited by applicant]
Au et al., Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood. May 1, 2008;111(9):4551-8.
[cited by applicant]
Aubin et al., Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials. Sep. 2010;31(27):6941-51.
[cited by applicant]
Azuma et al., Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/ll2rg-/- mice. Nat Biotechnol. Aug. 2007;25(8):903-10.
[cited by applicant]
Baranski et al., Geometric control of vascular networks to enhance engineered tissue integration and function. Proc Natl Acad Sci U S A. May 7, 2013;110(19):7586-91.
[cited by applicant]
Barron et al., Biological laser printing: a novel technique for creating heterogeneous 3-dimensional cell patterns. Biomed Microdevices. Jun. 2004;6(2):139-47.
[cited by applicant]
Baudin et al., A protocol for isolation and culture of human umbilical vein endothelial cells. Nat Protoc. 2007;2(3):481-5.
[cited by applicant]
Berry et al., High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. Dec. 1969;43(3):506-20.
[cited by applicant]
Bhatia et al., Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J. Nov. 1999;13(14):1883-900.
[cited by applicant]
Brophy et al., Rat hepatocyte spheroids formed by rocked technique maintain differentiated hepatocyte gene expression and function. Hepatology. Feb. 2009;49(2):578-86.
[cited by applicant]
Cao et al., Differentiation and Functional Comparison of Monocytes and Macrophages from hiPSCs with Peripheral Blood Derivatives. Stem Cell Reports. Jun. 11, 2019;12(6):1282-1297.
[cited by applicant]
Chan et al., Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation. Lab Chip. Aug. 21, 2010;10(16):2062-70.
[cited by applicant]
Chen et al., Humanized mice with ectopic artificial liver tissues. Proc Natl Acad Sci U S A. Jul. 19, 2011;108(29):11842-7.
[cited by applicant]
Chen et al., Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature. Tissue Eng Part A. Jun. 2009;15(6):1363-71.
[cited by applicant]
Chen et al., Rapid anastomosis of endothelial progenitor cell-derived vessels with host vasculature is promoted by a high density of cotransplanted fibroblasts. Tissue Eng Part A. Feb. 2010;16(2):585-94.
[cited by applicant]
Chen et al., Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. Pharm Res. Feb. 2007;24(2):258-64.
[cited by applicant]
Cheng et al., Engineered blood vessel networks connect to host vasculature via wrapping-and-tapping anastomosis. Blood. Oct. 27, 2011;118(17):4740-9.
[cited by applicant]
Cho et al., Layered patterning of hepatocytes in co-culture systems using microfabricated stencils. Biotechniques. Jan. 2010;48(1):47-52.
[cited by applicant]
Cho et al., Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel. Biomed Mater. Feb. 2009;4(1):011001, 7 pages.
[cited by applicant]
Choi et al., Patterning and transferring hydrogel-encapsulated bacterial cells for quantitative analysis of synthetically engineered genetic circuits. Biomaterials. Jan. 2012;33(2):624-33.
[cited by applicant]
Cleaver et al., Endothelial signaling during development. Nat Med. Jun. 2003;9(6):661-8.
[cited by applicant]
Collins, monodisperse. Collins English Dictionary, HarperCollins Publishers. 2 pages, (2014).
[cited by applicant]
Culver et al., Three-dimensional biomimetic patterning in hydrogels to guide cellular organization. Adv Mater. May 2, 2012;24(17):2344-8.
[cited by applicant]
Debbage et al., Intravital lectin perfusion analysis of vascular permeability in human micro- and macro-blood vessels. Histochem Cell Biol. Oct. 2001;116(4):349-59.
[cited by applicant]
Debbage et al., Lectin intravital perfusion studies in tumor-bearing mice: micrometer-resolution, wide-area mapping of microvascular labeling, distinguishing efficiently and inefficiently perfused microregions in the tu…
[cited by applicant]
Deforest et al., Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photoconjugation and photocleavage reactions. Nat Chem. Oct. 23, 2011;3(12):925-31.
[cited by applicant]
Dickinson et al., Guiding endothelial progenitor cell tube formation using patterned fibronectin surfaces. Soft Matter. 2010;6:5109-19.
[cited by applicant]
Ding et al., Endothelial-Derived Angiocrine Signals Induce and Sustain Regenerative Lung Alveolarization. Cell. Oct. 28, 2011; 147(3): 539-53.
[cited by applicant]
Ding et al., Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature. Nov. 11, 2010;468(7321):310-5.
[cited by applicant]
Douglas et al., Self-assembled cellular microarrays patterned using DNA barcodes. Lab Chip. Nov. 2007;7(11):1442-8.
[cited by applicant]
Du et al., Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs. Proc Natl Acad Sci U S A. Jul. 15, 2008;105(28):9522-7.
[cited by applicant]
Dunn et al., Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol Prog. May-Jun. 1991;7(3):237-45.
[cited by applicant]
Ennett et al., Tissue engineering strategies for in vivo neovascularisation. Expert Opin Biol Ther. Dec. 2002;2(8):805-18.
[cited by applicant]
Folkman, Looking for a good endothelial address. Cancer Cell. Mar. 2002;1(2):113-5.
[cited by applicant]
Francipane et a., Maturation of embryonic tissues in a lymph node: a new approach for bioengineering complex organs. Organogenesis. 2014;10(3):323-31.
[cited by applicant]
Franses et al., Stromal endothelial cells directly influence cancer progression. Sci Transl Med. Jan. 19, 2011;3(66):66ra5.
[cited by applicant]
Gartner et al., Programmed assembly of 3-dimensional microtissues with defined cellular connectivity. Proc Natl Acad Sci U S A. Mar. 24, 2009;106(12):4606-10.
[cited by applicant]
Gjorevski et al., Endogenous patterns of mechanical stress are required for branching morphogenesis. Integr Biol (Camb). Sep. 2010;2(9):424-34.
[cited by applicant]
Glicklis et al., Hepatocyte behavior within three-dimensional porous alginate scaffolds. Biotechnol Bioeng. Feb. 5, 2000;67(3):344-53.
[cited by applicant]
Hamada, In search of Turing in vivo: understanding Nodal and Lefty behavior. Dev Cell. May 15, 2012;22(5):911-2.
[cited by applicant]
Harding et al., An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice. PLoS One. Apr. 1, 2010;5(4):e9987, 15 pages.
[cited by applicant]
He et al., Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res. Jul. 11, 2003;93(1):32-9.
[cited by applicant]
Hristov et al., Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol. Jul. 1, 2003;23(7):1185-9.
[cited by applicant]
Hsiao et al., Direct cell surface modification with DNA for the capture of primary cells and the investigation of myotube formation on defined patterns. Langmuir. Jun. 16, 2009;25(12):6985-91.
[cited by applicant]
Hui et al., Micromechanical control of cell-cell interactions. Proc Natl Acad Sci U S A. Apr. 3, 2007;104(14):5722-6.
[cited by applicant]
Inman et al., Apical polarity in three-dimensional culture systems: where to now? J Biol. 2010;9(1):2, 5 pages.
[cited by applicant]
Intaglietta et al., Microvascular and tissue oxygen distribution. Cardiovasc Res. Oct. 1996;32(4):632-43.
[cited by applicant]
Jain, Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng. 1999;1:241-63.
[cited by applicant]
Jakab et al., Engineering biological structures of prescribed shape using self-assembling multicellular systems. Proc Natl Acad Sci U S A. Mar. 2, 2004;101(9):2864-9.
[cited by applicant]
Jakab et al., Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication. Jun. 2010;2(2):022001, 34 pages.
[cited by applicant]
Jeong et al., “Living” microvascular stamp for patterning of functional neovessels; orchestrated control of matrix property and geometry. Adv Mater. Jan. 3, 2012;24(1):58-63.
[cited by applicant]
Kachouie et al., Directed assembly of cell-laden hydrogels for engineering functional tissues. Organogenesis. Oct.-Dec. 2010;6(4):234-44.
[cited by applicant]
Kaji et al., Engineering systems for the generation of patterned co-cultures for controlling cell-cell interactions. Biochim Biophys Acta. Mar. 2011;1810(3):239-50.
[cited by applicant]
Kang et al., Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion. Blood. Dec. 15, 2011;118(25):6718-21.
[cited by applicant]
Kaufman-Francis et al., Engineered vascular beds provide key signals to pancreatic hormone-producing cells. PLoS One. 2012;7(7):e40741, 10 pages.
[cited by applicant]
Kaufmann et al., Highly porous polymer matrices as a three-dimensional culture system for hepatocytes. Cell Transplant. Sep.-Oct. 1997;6(5):463-8.
[cited by applicant]
Khademhosseini et al., Progress in tissue engineering. Sci Am. May 2009;300(5):64-71.
[cited by applicant]
Khetani et al., Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling. Hepatology. Sep. 2004;40(3):545-54.
[cited by applicant]
Khetani et al., Microscale culture of human liver cells for drug development. Nat Biotechnol. Jan. 2008;26(1):120-6.
[cited by applicant]
Khetani et al., T-cadherin modulates hepatocyte functions in vitro. FASEB J. Nov. 2008;22(11):3768-75.
[cited by applicant]
Kloxin et al., Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science. Apr. 3, 2009;324(5923):59-63.
[cited by applicant]
Kneser et al., Long-term differentiated function of heterotopically transplanted hepatocytes on three-dimensional polymer matrices. J Biomed Mater Res. Dec. 15, 1999;47(4):494-503.
[cited by applicant]
Koffler et al., Improved vascular organization enhances functional integration of engineered skeletal muscle grafts. Proc Natl Acad Sci U S A. Sep. 6, 2011;108(36):14789-94. Including Correction, PNAS. Jan. 24, 2012;109…
[cited by applicant]
Koike et al., Tissue engineering: creation of long-lasting blood vessels. Nature. Mar. 11, 2004;428(6979):138-9.
[cited by applicant]
Komori et al., The mouse lymph node as an ectopic transplantation site for multiple tissues. Nat Biotechnol. Oct. 2012;30(10):976-83.
[cited by applicant]
Lammert et al., Induction of pancreatic differentiation by signals from blood vessels. Science. Oct. 19, 2001;294(5542):564-7.
[cited by applicant]
Lammert et al., Role of endothelial cells in early pancreas and liver development. Mech Dev. Jan. 2003;120(1):59-64.
[cited by applicant]
Landry et al., Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. J Cell Biol. Sep. 1985;101(3):914-23.
[cited by applicant]
Lang et al., Transplantation of mouse embryonic stem cells into the cochlea of an auditory-neuropathy animal model: effects of timing after injury. J Assoc Res Otolaryngol. Jun. 2008;9(2):225-40.
[cited by applicant]
Laube et al., Re-programming of newt cardiomyocytes is induced by tissue regeneration. J Cell Sci. Nov. 15, 2006;119(Pt 22):4719-29.
[cited by applicant]
Lee et al., Controlled growth factor release from synthetic extracellular matrices. Nature. Dec. 21-28, 2000;408(6815):998-1000.
[cited by applicant]
Lee et al., Local delivery of basic fibroblast growth factor increases both angiogenesis and engraftment of hepatocytes in tissue-engineered polymer devices. Transplantation. May 27, 2002;73(10):1589-93.
[cited by applicant]
Leight et al., Manipulation of 3D Cluster Size and Geometry by Release from 2D Micropatterns. Cell Mol Bioeng. Sep. 1, 2012;5(3):299-306.
[cited by applicant]
Levenberg et al., Engineering vascularized skeletal muscle tissue. Nat Biotechnol. Jul. 2005;23(7):879-84.
[cited by applicant]
Li et al., DNA-templated assembly of droplet-derived PEG microtissues. Lab Chip. Sep. 7, 2011;11(17):2967-75.
[cited by applicant]
Li et al., The dose of growth factors influences the synergistic effect of vascular endothelial growth factor on bone morphogenetic protein 4-induced ectopic bone formation. Tissue Eng Part A. Aug. 2009;15(8):2123-33.
[cited by applicant]
Liu et al., Hepatocyte cocultures with endothelial cells and fibroblasts on micropatterned fibrous mats to promote liver-specific functions and capillary formation capabilities. Biomacromolecules. Mar. 10, 2014;15(3):10…
[cited by applicant]
Liu et al., Three-Dimensional Photopatterning of Hydrogels Containing Living Cells. Biomedical Microdevices. 2002;4(4):257-266.
[cited by applicant]
Lovett et al., Vascularization strategies for tissue engineering. Tissue Eng Part B Rev. Sep. 2009;15(3):353-70.
[cited by applicant]
Lu et al., Three-dimensional co-culture of rat hepatocyte spheroids and NIH/3T3 fibroblasts enhances hepatocyte functional maintenance. Acta Biomater. Jul. 2005;1(4):399-410.
[cited by applicant]
Macneil et al., Progress and opportunities for tissue-engineered skin. Nature. Feb. 22, 2007;445(7130):874-80.
[cited by applicant]
Mailleux et al., Lumen formation during mammary epithelial morphogenesis: insights from in vitro and in vivo models. Cell Cycle. Jan. 1, 2008;7(1):57-62.
[cited by applicant]
March et al., Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology. Sep. 2009;50(3):920-8.
[cited by applicant]
Matsumoto et al., Liver organogenesis promoted by endothelial cells prior to vascular function. Science. Oct. 19, 2001;294(5542):559-63.
[cited by applicant]
Matsumura et al., Establishment of an immortalized human-liver endothelial cell line with SV40T and hTERT. Transplantation. May 15, 2004;77(9):1357-65.
[cited by applicant]
Maurice et al., Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J. Jan. 6, 1992;6(2):752-8.
[cited by applicant]
Mcguigan et al., Vascularized organoid engineered by modular assembly enables blood perfusion. Proc Natl Acad Sci U S A. Aug. 1, 2006;103(31):11461-6.
[cited by applicant]
Mei et al., Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice. Cell Transplant. 2009;18(1):101-10.
[cited by applicant]
Melero-Martin et al., Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res. Jul. 18, 2008;103(2):194-202.
[cited by applicant]
Mikos et al., Engineering complex tissues. Tissue Eng. Dec. 2006;12(12):3307-39.
[cited by applicant]
Miller et al., Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater. Sep. 2012;11(9):768-74.
[cited by applicant]
Mironov et al., Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol. Apr. 2003;21(4):157-61.
[cited by applicant]
Mironov et al., Organ printing: tissue spheroids as building blocks. Biomaterials. Apr. 2009;30(12):2164-74.
[cited by applicant]
Mooney et al., Growing new organs. Sci Am. Apr. 1999;280(4):60-5.
[cited by applicant]
Moscona, Rotation-mediated histogenetic aggregation of dissociated cells. A quantifiable approach to cell interactions in vitro. Exp Cell Res. Jan. 1961;22:455-75.
[cited by applicant]
Muller at al., Extracellular movement of signaling molecules. Dev Cell. Jul. 19, 2011;21(1):145-58.
[cited by applicant]
Muller et al., Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system. Science. May 11, 2012;336(6082):721-4.
[cited by applicant]
Nahmias et al., Integration of technologies for hepatic tissue engineering. Adv Biochem Eng Biotechnol. 2007;103:309-29.
[cited by applicant]
Nahmias et al., Laser-guided direct writing for three-dimensional tissue engineering. Biotechnol Bioeng. Oct. 20, 2005;92(2):129-36.
[cited by applicant]
Nelson et al., Microstructured extracellular matrices in tissue engineering and development. Curr Opin Biotechnol. Oct. 2006;17(5):518-23.
[cited by applicant]
Nelson et al., Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science. Oct. 13, 2006;314(5797):298-300.
[cited by applicant]
Nikkhah et al., Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials. Dec. 2012;33(35):9009-18.
[cited by applicant]
Nikolova et al., The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation. Dev Cell. Mar. 2006;10(3):397-405.
[cited by applicant]
Nomi et al., Principals of neovascularization for tissue engineering. Mol Aspects Med. Dec. 2002;23(6):463-83.
[cited by applicant]
Ohashi et al., Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases. Hepatology. Jan. 2005;41(1):132-40.
[cited by applicant]
Omidan et al., Swelling and mechanical properties of modified hema-based superporous hydrogels. J Bioact Compat Polym. Sep. 2010;25:483-97.
[cited by applicant]
Panda et al., Stop-flow lithography to generate cell-laden microgel particles. Lab Chip. Jul. 2008;8(7):1056-61.
[cited by applicant]
Parenteau, Commercial development of cell-based therapeutics: strategic considerations along the drug to tissue spectrum. Regen Med. Jul. 2009;4(4):601-11.
[cited by applicant]
Partial Supplementary European Search Report for Applicatio No. 13817119.4, dated Feb. 24, 2016.
[cited by applicant]
Peshwa et al., Mechanistics of formation and ultrastructural evaluation of hepatocyte spheroids. In Vitro Cell Dev Biol Anim. Apr. 1996;32(4):197-203.
[cited by applicant]
Phelps et al., Engineering more than a cell: vascularization strategies in tissue engineering. Curr Opin Biotechnol. Oct. 2010;21(5):704-9.
[cited by applicant]
Pittman et al., Influence of microvascular architecture on oxygen exchange in skeletal muscle. Microcirculation. May 1995;2(1):1-18.
[cited by applicant]
Qiu et al., Generation of Uniformly Sized Alginate Microparticles for Cell Encapsulation by Using a Soft-Lithography Approach. Advanced Materials. May 15, 2007;19(12):1603-1607.
[cited by applicant]
Radisic et al., High-density seeding of myocyte cells for cardiac tissue engineering. Biotechnol Bioeng. May 20, 2003;82(4):403-14.
[cited by applicant]
Raghavan et al., Geometrically controlled endothelial tubulogenesis in micropatterned gels. Tissue Eng Part A. Jul. 2010;16(7):2255-63.
[cited by applicant]
Rago et al., Encapsulated arrays of self-assembled microtissues: an alternative to spherical microcapsules. Tissue Eng Part A. Feb. 2009;15(2):387-95.
[cited by applicant]
Ramanan et al., Engineered Ectopic Human Livers Organize and Proliferate in Vivo in Response to Regenerative Cues. BMES, Biomedical Engineering Society 2015 Annual Meeting, Poster Presentation. 1 page, (2015).
[cited by applicant]
Reid et al., Extracellular matrix gradients in the space of Disse: relevance to liver biology. Hepatology. Jun. 1992;15(6):1198-203.
[cited by applicant]
Richardson et al., Polymeric system for dual growth factor delivery. Nat Biotechnol. Nov. 2001;19(11):1029-34.
[cited by applicant]
Rnjak et al., Primary human dermal fibroblast interactions with open weave three-dimensional scaffolds prepared from synthetic human elastin. Biomaterials. Nov. 2009;30(32):6469-77.
[cited by applicant]
Roh et al., Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling. Proc Natl Acad Sci U S A. Mar. 9, 2010;107(10):4669-74.
[cited by applicant]
Rosmorduc et al., Hypoxia: a link between fibrogenesis, angiogenesis, and carcinogenesis in liver disease. Semin Liver Dis. Aug. 2010;30(3):258-70.
[cited by applicant]
Sakai et al., A new bioartificial liver using porcine hepatocyte spheroids in high-cell-density suspension perfusion culture: in vitro performance in synthesized culture medium and in 100% human plasma. Cell Transplant.…
[cited by applicant]
Satsix, Needle guage comparison chart. Retrieved online at: https://m.blog.naver.com/PostView.naver?isHttpsRedirect=true&blogId=satsix&logNo=104709066. 3 pages, (2010).
[cited by applicant]
Schwartz et al., Modeling hepatitis C virus infection using human induced pluripotent stem cells. Proc Natl Acad Sci U S A. Feb. 14, 2012;109(7):2544-8.
[cited by applicant]
Seglen et al., Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29-83.
[cited by applicant]
Seo et al., Enhanced liver functions of hepatocytes cocultured with Nih 3T3 in the alginate/galactosylated chitosan scaffold. Biomaterials. Mar. 2006;27(8):1487-95.
[cited by applicant]
Si-Tayeb et al., Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology. Jan. 2010;51(1):297-305.
[cited by applicant]
Smith et al., Locally enhanced angiogenesis promotes transplanted cell survival. Tissue Eng. Jan.-Feb. 2004;10(1-2):63-71.
[cited by applicant]
Stevens et al., In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci U S A. Aug. 9, 2005;102(32):11450-5.
[cited by applicant]
Stevens et al., InVERT molding for scalable control of tissue microarchitecture. Nat Commun. 2013;4;1847.
[cited by applicant]
Stevens et al., Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue. Proc Natl Acad Sci U S A. Sep. 29, 2009;106(39):16568-73.
[cited by applicant]
Takahashi et al., Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. Aug. 25, 2006;126(4):663-76.
[cited by applicant]
Takebe et al., Engineering of human hepatic tissue with functional vascular networks. Organogenesis. Apr.-Jun. 2014;10(2):260-7.
[cited by applicant]
Takebe et al., Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. Nat Protoc. Feb. 2014;9(2):396-409.
[cited by applicant]
Takebe et al., Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. Jul. 25, 2013;499(7459):481-4.
[cited by applicant]
Tamai et al., Characterization of a liver organoid tissue composed of hepatocytes and fibroblasts in dense collagen fibrils. Tissue Eng Part A. Nov. 2013;19(21-22):2527-35.
[cited by applicant]
Tan et al., Layer-by-layer microfluidics for biomimetic three-dimensional structures. Biomaterials. Mar.-Apr. 2004;25(7-8):1355-64.
[cited by applicant]
Tan et al., Monodisperse Alginate Hydrogel Microbeads for Cell Encapsulation. Adv Mater. 2007;19:2696-2701.
[cited by applicant]
Tateno et al., Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J Pathol. Sep. 2004;165(3):901-12.
[cited by applicant]
Tekin et al., Responsive micromolds for sequential patterning of hydrogel microstructures. J Am Chem Soc. Aug. 24, 2011;133(33):12944-7.
[cited by applicant]
Traktuev et al., Robust functional vascular network formation in vivo by cooperation of adipose progenitor and endothelial cells. Circ Res. Jun. 19, 2009;104(12):1410-20.
[cited by applicant]
Tsang et al., Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J. Mar. 2007;21(3):790-801.
[cited by applicant]
Tsang et al., Three-dimensional tissue fabrication. Adv Drug Deliv Rev. Sep. 22, 2004;56(11):1635-47.
[cited by applicant]
Tsuda et al., Cellular control of tissue architectures using a three-dimensional tissue fabrication technique. Biomaterials. Nov. 2007;28(33):4939-46.
[cited by applicant]
Ulbright et al., On the biodegradability of polyethylene glycol, polypeptoids and poly(2-oxazoline)s. Biomaterials. Jun. 2014;35(17):4848-61.
[cited by applicant]
Underhill et al., Assessment of hepatocellular function within PEG hydrogels. Biomaterials. Jan. 2007;28(2):256-70.
[cited by applicant]
Ungrin et al., Reproducible, ultra high-throughput formation of multicellular organization from single cell suspension-derived human embryonic stem cell aggregates. PLoS One. Feb. 13, 2008;3(2):e1565, 12 pages.
[cited by applicant]
US Department of Health and Human Services, The Need is Real: Data. National Organ Transplant Waiting List Report. http://organdonor.gov/about/data.html. 3 pages, retrieved Oct. 16, 2015.
[cited by applicant]
Uyama et al., Hepatocyte transplantation using biodegradable matrices in ascorbic acid-deficient rats: comparison with heterotopically transplanted liver grafts. Transplantation. May 15, 2001;71(9):1226-31.
[cited by applicant]
Vacanti et al., Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet. Jul. 1999;354 Suppl 1:SI32-4.
[cited by applicant]
Vacanti, Tissue engineering and the road to whole organs. Br J Surg. Apr. 2012;99(4):451-3.
[cited by applicant]
Valignat et al., Reversible self-assembly and directed assembly of DNA-linked micrometer-sized colloids. Proc Natl Acad Sci U S A. Mar. 22, 2005;102(12):4225-9.
[cited by applicant]
Vanbuskirk et al., Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design. Proc Natl Acad Sci U S A. Aug. 4, 2009;106(31):13004-9.
[cited by applicant]
Weber et al., Cell-matrix interactions improve beta-cell survival and insulin secretion in three-dimensional culture. Tissue Eng Part A. Dec. 2008;14(12):1959-68.
[cited by applicant]
White et al., Longitudinal in vivo imaging to assess blood flow and oxygenation in implantable engineered tissues. Tissue Eng Part C Methods. Sep. 2012;18(9):697-709.
[cited by applicant]
Williams et al., Autocrine-controlled formation and function of tissue-like aggregates by primary hepatocytes in micropatterned hydrogel arrays. Tissue Eng Part A. Apr. 2011;17(7-8):1055-68.
[cited by applicant]
Wong et al., Concave microwell based size-controllable hepatosphere as a three-dimensional liver tissue model. Biomaterials. Nov. 2011;32(32):8087-96.
[cited by applicant]
Wylie et al., Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. Nat Mater. Oct. 2011;10(10):799-806.
[cited by applicant]
Yeh et al., Micromolding of shape-controlled, harvestable cell-laden hydrogels. Biomaterials. Nov. 2006;27(31):5391-8.
[cited by applicant]
Yokoyama et al., In vivo engineering of metabolically active hepatic tissues in a neovascularized subcutaneous cavity. Am J Transplant. Jan. 2006;6(1):50-9.
[cited by applicant]
Zhang et al., In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. Dec. 2001;19(12):1129-33.
[cited by applicant]
Zhou et al., Neural cell injury microenvironment induces neural differentiation of human umbilical cord mesenchymal stem cells. Neural Regen Res. Dec. 5, 2012;7(34):2689-97.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2011/055179, dated Apr. 9, 2013, 12 pages.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2012/037656, dated Nov. 12, 2013, 7 pages.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2013/028345, dated Sep. 2, 2014, 6 pages.
[cited by applicant]
International Preliminary Report on Patentability for Application No. PCT/US2016/055972, dated Apr. 10, 2018, 6 pages.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2011/055179, dated May 23, 2012, 17 pages.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2012/037656, dated Oct. 17, 2012, 9 pages.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2013/028345, dated May 24, 2013, 9 pages.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2013/049933, dated Dec. 17, 2013, 10 pages.
[cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2016/055972, dated Jan. 10, 2017, 8 pages.
[cited by applicant]
Invitation to Pay Additional Fees for Application No. PCT/US2011/055179, dated Oct. 13, 2011, 4 pages.
[cited by applicant]