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Vascular Networks Within 3D Printed and Engineered Tissues

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3D Printing and Biofabrication

Part of the book series: Reference Series in Biomedical Engineering ((TIENRE))

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Abstract

In order to scale benchtop tissue mimics into viable constructs of clinically relevant dimensions, these structures must contain internal vascular networks to support convective mass transport. Without vessels to support perfusion culture, encapsulated cells located farther than 200 μm from the outer surface of a construct will quickly die due to the diffusional limits of oxygen and small molecule nutrients. By endowing artificial tissues with hollow vessels, researchers have made exciting progress towards the longitudinal maintenance of cellular function in large, dense tissues. But the field currently lacks standardized platforms and protocols to fabricate highly vascularized constructs in a rapid and cost-effective manner, which has left the literature base to become crowded with custom apparatus and diverse technical schemes. Here we highlight some promising, contemporary strategies for the vascularization of 3D printed and engineered tissues. We discuss the advantages and limitations of various fabrication platforms in the field, making note of desirable properties such as high spatial resolution, freely tunable 3D architecture, and the presence of discrete fluidic ports. With clinical targets in mind, this overview concludes with a brief survey of progress towards fluidic integration with the circulatory system in vivo.

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References

  • Arcaute K, Mann BK, Wicker RB (2006) Stereolithography of three-dimensional bioactive poly(ethylene glycol) constructs with encapsulated cells. Ann Biomed Eng 34:1429–1441. doi:10.1007/s10439-006-9156-y

    Article  PubMed  Google Scholar 

  • Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB (2006) Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246. doi:10.1016/S0140-6736(06)68438-9

    Article  PubMed  Google Scholar 

  • Bertassoni L, Cardoso JC, Manoharan V, Cristino AL, Bhise NS, Araujo WA, Zorlutuna P, Vrana NE, Ghaemmaghami AM, Dokmeci MR, Khademhosseini A (2014a) Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication 6:24105. doi:10.1088/1758-5082/6/2/024105

    Article  Google Scholar 

  • Bertassoni L, Cecconi M, Manoharan V, Nikkhah M, Hjortnaes J, Cristino AL, Barabaschi G, Demarchi D, Dokmeci MR, Yang Y, Khademhosseini A (2014b) Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14:2202–2211. doi:10.1039/c4lc00030g

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhattacharjee T, Zehnder SM, Rowe KG, Jain S, Nixon RM, Sawyer WG, Angelini TE (2015) Writing in the granular gel medium. Sci Adv 1:e1500655. doi:10.1126/sciadv.1500655

    Article  PubMed  PubMed Central  Google Scholar 

  • Bohorquez M, Koch C, Trygstad T, Pandit N (1999) A study of the temperature-dependent micellization of Pluronic F127. J Colloid Interface Sci 216:34–40. doi:10.1006/jcis.1999.6273

    Article  CAS  PubMed  Google Scholar 

  • Bryant SJ, Cuy JL, Hauch KD, Ratner BD (2007) Photo-patterning of porous hydrogels for tissue engineering. Biomaterials 28:2978–2986. doi:10.1016/j.biomaterials.2006.11.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cabodi M, Choi NW, Gleghorn JP, Lee CSD, Bonassar LJ, Stroock AD (2005) A microfluidic biomaterial. J Am Chem Soc 127:13788–13789. doi:10.1021/ja054820t

    Article  CAS  PubMed  Google Scholar 

  • Christensen K, Xu C, Chai W, Zhang Z, Fu J, Huang Y (2015) Freeform inkjet printing of cellular structures with bifurcations. Biotechnol Bioeng 112:1047–1055. doi:10.1002/bit.25501

    Article  CAS  PubMed  Google Scholar 

  • Chrobak KM, Potter DR, Tien J (2006) Formation of perfused, functional microvascular tubes in vitro. Microvasc Res 71:185–196. doi:10.1016/j.mvr.2006.02.005

    Article  CAS  PubMed  Google Scholar 

  • Costantini M, Colosi C, Mozetic P, Jaroszewicz J, Tosato A, Rainer A, Trombetta M, Wojciech Ś, Dentini M, Barbetta A (2016) Correlation between porous texture and cell seeding efficiency of gas foaming and microfluidic foaming scaffolds. Mater Sci Eng C 62:668–677. doi:10.1016/j.msec.2016.02.010

    Article  CAS  Google Scholar 

  • Dore-Duffy P, Katychev A, Wang X, Van Buren E (2006) CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 26:613–624. doi:10.1038/sj.jcbfm.9600272

    Article  CAS  PubMed  Google Scholar 

  • Galie PA, Nguyen D-HT, Choi CK, Cohen DM, Janmey PA, Chen CS (2014) Fluid shear stress threshold regulates angiogenic sprouting. Proc Natl Acad Sci U S A 111:7968–7973. doi:10.1073/pnas.1310842111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Q, He Y, Fu J, Liu A, Ma L (2015) Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery. Biomaterials 61:203–215. doi:10.1016/j.biomaterials.2015.05.031

    Article  CAS  PubMed  Google Scholar 

  • Ghassemi P, Wang J, Melchiorri AJ, Ramella-Roman JC, Mathews SA, Coburn JC, Sorg BS, Chen Y, Pfefer TJ (2015) Rapid prototyping of biomimetic vascular phantoms for hyperspectral reflectance imaging. J Biomed Opt 20:121312. doi:10.1117/1.JBO.20.12.121312

    Article  PubMed  PubMed Central  Google Scholar 

  • Golden AP, Tien J (2007) Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 7:720–725. doi:10.1039/b618409j

    Article  CAS  PubMed  Google Scholar 

  • Hasan A, Paul A, Memic A, Khademhosseini A (2015) A multilayered microfluidic blood vessel-like structure. Biomed Microdevices 17:9993. doi:10.1007/s10544-015-9993-2

    Article  Google Scholar 

  • Haynesworth SE, Goshima J, Goldberg VM, Caplan AI (1992) Characterization of cells with osteogenic potential from human marrow. Bone 13:81–88. doi:10.1016/8756-3282(92)90364-3

    Article  CAS  PubMed  Google Scholar 

  • Heimbach D, Luterman A, Burke J, Cram A, Herndon D, Hunt J, Jordan M, McManus W, Solem L, Warden G (1988) Artificial dermis for major burns. A multi-center randomized clinical trial. Ann Surg 208:313–320. doi:10.1097/00000658-198809000-00008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hinton TJ, Jallerat Q, Palchesko RN, Park JH, Grodzicki MS, Shue H, Ramadan MH, Hudson AR, Feinberg AW (2015) Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci Adv 1:1–10. doi:10.1126/sciadv.1500758

    Article  Google Scholar 

  • Horinaka J ichi, Urabayashi Y, Wang X, Takigawa T (2014) Molecular weight between entanglements for κ- and ι-carrageenans in an ionic liquid. Int J Biol Macromol 69:416–419. doi: 10.1016/j.ijbiomac.2014.05.076

    Google Scholar 

  • Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP (1997) Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64:295–312. doi:10.1002/(sici)1097-4644(199702)64:2<295::aid-jcb12>3.0.co;2-i

    Article  CAS  PubMed  Google Scholar 

  • Jakab K, Norotte C, Damon B, Marga F, Neagu A, Besch-Williford CL, Kachurin A, Church KH, Park H, Mironov V, Markwald R, Vunjak-Novakovic G, Forgacs G (2008) Tissue engineering by self-assembly of cells printed into topologically defined structures. Tissue Eng Part A 14:413–421. doi:10.1089/ten.2007.0173

    Article  CAS  PubMed  Google Scholar 

  • Jeffries EM, Nakamura S, Lee K-W, Clampffer J, Ijima H, Wang Y (2014) Micropatterning electrospun scaffolds to create intrinsic vascular networks. Macromol Biosci 14:1514–1520. doi:10.1002/mabi.201400306

    Article  CAS  PubMed  Google Scholar 

  • Jeon JS, Bersini S, Whisler JA, Chen MB, Dubini G, Charest JL, Moretti M, Kamm RD (2014) Generation of 3D functional microvascular networks with human mesenchymal stem cells in microfluidic systems. Integr Biol 6:555–563. doi:10.1039/C3IB40267C

    Article  CAS  Google Scholar 

  • Jia W, Gungor-Ozkerim PS, Zhang YS, Yue K, Zhu K, Liu W, Pi Q, Byambaa B, Dokmeci MR, Shin SR, Khademhosseini A (2016) Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. Biomaterials 106:58–68. doi:10.1016/j.biomaterials.2016.07.038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jun H-W, West JL (2005) Endothelialization of microporous YIGSR/PEG-modified polyurethaneurea. Tissue Eng 11:1133–1140. doi:10.1089/ten.2005.11.1133

    Article  CAS  PubMed  Google Scholar 

  • Kang H-W, Lee SJ, Ko IK, Kengla C, Yoo JJ, Atala A (2016) A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol. doi:10.1038/nbt.3413

    PubMed Central  Google Scholar 

  • Kibbe MR, Martinez J, Popowich DA, Kapadia MR, Ahanchi SS, Aalami OO, Jiang Q, Webb AR, Yang J, Carroll T, Ameer GA (2010) Citric acid-based elastomers provide a biocompatible interface for vascular grafts. J Biomed Mater Res A 93:314–324. doi:10.1002/jbm.a.32537

    PubMed  Google Scholar 

  • Kim S, Kawai T, Wang D, Yang Y (2016) Engineering a dual-layer chitosan-lactide hydrogel to create endothelial cell aggregate-induced microvascular networks in vitro and increase blood perfusion in vivo. ACS Appl Mater Interfaces 8:19245–19255. doi:10.1021/acsami.6b04431

    Article  CAS  PubMed  Google Scholar 

  • King KR, Wang CCJ, Kaazempur-Mofrad MR, Vacanti JP, Borenstein JT (2004) Biodegradable microfluids. Adv Mater 16:2007–2012. doi:10.1002/adma.200306522

    Article  CAS  Google Scholar 

  • Kinstlinger IS, Miller J (2016) 3D-printed fluidic networks as vasculature for engineered tissue. Lab Chip 16:2025–2043. doi:10.1039/C6LC00193A

    Article  CAS  PubMed  Google Scholar 

  • Kinstlinger IS, Bastian A, Paulsen SJ, Hwang DH, Ta AH, Yalacki DR, Schmidt T, Miller JS (2016) Open-Source Selective Laser Sintering (OpenSLS) of nylon and biocompatible polycaprolactone. PLoS One 11:1–25. doi:10.1371/journal.pone.0147399

    Article  Google Scholar 

  • Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA (2014) 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater 26:3124–3130. doi:10.1002/adma.201305506

    Article  CAS  PubMed  Google Scholar 

  • Kolesky DB, Homan KA, Skylar-Scott MA, Lewis JA (2016) Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci U S A 201521342. doi:10.1073/pnas.1521342113

    Google Scholar 

  • Langer R, Folkman J (1976) Polymers for the sustained release of proteins and other macromolecules. Nature 263:797–800

    Article  CAS  PubMed  Google Scholar 

  • Lenard A, Daetwyler S, Betz C, Ellertsdottir E, Belting HG, Huisken J, Affolter M (2015) Endothelial cell self-fusion during vascular pruning. PLoS Biol 13:1–25. doi:10.1371/journal.pbio.1002126

    Article  Google Scholar 

  • Liu Tsang V, Chen AA, Cho LM, Jadin KD, Sah RL, DeLong S, West JL, Bhatia SN (2007) Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J 21:790–801. doi:10.1096/fj.06-7117com

    Article  PubMed  Google Scholar 

  • Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, Cogan TA, Dodson A, Martorell J, Bellini S, Parnigotto PP, Dickinson SC, Hollander AP, Mantero S, Conconi MT, Birchall MA (2008) Clinical transplantation of a tissue-engineered airway. Lancet 372:2023–2030. doi:10.1016/S0140-6736(08)61598-6

    Article  PubMed  Google Scholar 

  • McGuigan AP, Sefton MV (2007) The influence of biomaterials on endothelial cell thrombogenicity. Biomaterials 28:2547–2571. doi:10.1016/j.biomaterials.2007.01.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer W, Engelhardt S, Novosel E, Elling B, Wegener M, Krüger H (2012) Soft polymers for building up small and smallest blood supplying systems by stereolithography. J Funct Biomater 3:257–268. doi:10.3390/jfb3020257

    Article  PubMed  PubMed Central  Google Scholar 

  • Miller JS, Burdick JA (2016) Editorial: special issue on 3D printing of biomaterials. ACS Biomater Sci Eng 2:1658–1661. doi:10.1021/acsbiomaterials.6b00566

    Article  CAS  Google Scholar 

  • Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen D-HT, Cohen DM, Toro E, Chen AA, Galie PA, Yu X, Chaturvedi R, Bhatia SN, Chen CS (2012) Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater 11:768–774. doi:10.1038/nmat3357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura M, Nishiyama Y, Henmi C, Iwanaga S, Nakagawa H, Yamaguchi K, Akita K, Mochizuki S, Takiura K (2008) Ink jet three-dimensional digital fabrication for biological tissue manufacturing: analysis of alginate microgel beads produced by ink jet droplets for three dimensional tissue fabrication. J Imaging Sci Technol 52:1–15. doi:10.2352/J.ImagingSci.Technol

    Article  Google Scholar 

  • Nguyen D-HT, Stapleton SC, Yang MT, Cha SS, Choi CK, Galie PA, Chen CS (2013) Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. Proc Natl Acad Sci U S A 110:6712–6717. doi:10.1073/pnas.1221526110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, Tano Y (2004) Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med 351:1187–1196. doi:10.1056/NEJMoa040455

    Article  CAS  PubMed  Google Scholar 

  • Nishiyama Y, Nakamura M, Henmi C, Yamaguchi K, Mochizuki S, Nakagawa H, Takiura K (2009) Development of a three-dimensional bioprinter: construction of cell supporting structures using hydrogel and state-of-the-art inkjet technology. J Biomech Eng 131:35001. doi:10.1115/1.3002759

    Article  Google Scholar 

  • Oheim M, Michael DJ, Geisbauer M, Madsen D, Chow RH (2006) Principles of two-photon excitation fluorescence microscopy and other nonlinear imaging approaches. Adv Drug Deliv Rev 58:788–808. doi:10.1016/j.addr.2006.07.005

    Article  CAS  PubMed  Google Scholar 

  • Pham QP, Sharma U, Mikos AG (2006) Electrospun poly (ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules 7:2796–2805. doi:10.1021/bm060680j

    Article  CAS  PubMed  Google Scholar 

  • Ratner B, Hoffman A, Schoen F, Lemons J (2004) Biomaterials science: an introduction to materials in medicine, 2nd edn. Academic, Cambridge

    Google Scholar 

  • Raya-Rivera A, Esquiliano DR, Yoo JJ, Lopez-Bayghen E, Soker S, Atala A (2011) Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Lancet 377:1175–1182. doi:10.1016/S0140-6736(10)62354-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Razavi MS, Shirani E, Salimpour MR, Kassab GS (2014) Constructal law of vascular trees for facilitation of flow. PLoS One 9:e116260. doi:10.1371/journal.pone.0116260

    Article  PubMed  PubMed Central  Google Scholar 

  • Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–684

    Article  CAS  PubMed  Google Scholar 

  • Schüller-Ravoo S, Zant E, Feijen J, Grijpma DW (2014) Preparation of a designed poly(trimethylene carbonate) microvascular network by stereolithography. Adv Healthc Mater 3:2004–2011. doi:10.1002/adhm.201400363

    Article  PubMed  Google Scholar 

  • Sooppan R, Paulsen SJ, Han J, Ta AH, Dinh P, Gaffey AC, Venkataraman C, Trubelja A, Hung G, Miller JS, Atluri P (2016) In vivo anastomosis and perfusion of a three-dimensionally-printed construct containing microchannel networks. Tissue Eng Part C Methods 22. doi:10.1089/ten.tec.2015.0239

    Google Scholar 

  • Stachowiak AN, Bershteyn A, Tzatzalos E, Irvine DJ (2005) Bioactive hydrogels with an ordered cellular structure combine interconnected macroporosity and robust mechanical properties. Adv Mater 17:399–403. doi:10.1002/adma.200400507

    Article  CAS  Google Scholar 

  • Suri S, Han L-H, Zhang W, Singh A, Chen S, Schmidt CE (2011) Solid freeform fabrication of designer scaffolds of hyaluronic acid for nerve tissue engineering. Biomed Microdevices 13:983–993. doi:10.1007/s10544-011-9568-9

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. doi:10.1016/j.cell.2006.07.024

    Article  CAS  PubMed  Google Scholar 

  • Tamayol A, Najafabadi AH, Aliakbarian B, Arab-Tehrany E, Akbari M, Annabi N, Juncker D, Khademhosseini A (2015) Hydrogel templates for rapid manufacturing of bioactive fibers and 3D constructs. Adv Healthc Mater. doi:10.1002/adhm.201500492

    PubMed Central  Google Scholar 

  • Trachtenberg JE, Mountziaris PM, Miller JS, Wettergreen M, Kasper FK, Mikos AG (2014) Open-source three-dimensional printing of biodegradable polymer scaffolds for tissue engineering. J Biomed Mater Res A 4326–4335. doi:10.1002/jbm.a.35108

    Google Scholar 

  • Vacanti CA (2006) The history of tissue engineering. J Cell Mol Med 10:569–576. doi:10.1111/j.1582-4934.2006.tb00421.x

    Article  PubMed  Google Scholar 

  • Wang EA, Rosen V, D’Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM, LaPan P et al (1990) Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci U S A 87:2220–2224. doi:10.1073/pnas.87.6.2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Phan DTT, George SC, Hughes CCW, Lee AP (2015) Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab Chip 16:282–290. doi:10.1039/C5LC01050K

    Article  Google Scholar 

  • Whang K, Tsai DC, Nam EK, Aitken M, Sprague SM, Patel PK, Healy KE (1998) Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds. J Biomed Mater Res 42:491–499. doi:10.1002/(SICI)1097-4636(19981215)42:4<491::AID-JBM3>3.0.CO;2-F

    Article  CAS  PubMed  Google Scholar 

  • Wu W, Deconinck A, Lewis JA (2011) Omnidirectional printing of 3D microvascular networks. Adv Mater 23:178–183. doi:10.1002/adma.201004625

    Article  Google Scholar 

  • Yannas V, Burke JF, Orgill DP, Skrabut EM (1982) Wound tissue can utilize a polymeric template to synthesize a functional extension of skin. Science 215:174–176. doi:10.1126/science.7031899

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Yu Y, Akkouch A, Dababneh A, Dolati F, Ozbolat IT (2015) In vitro study of directly bioprinted perfusable vasculature conduits. Biomater Sci 3:134–143. doi:10.1039/C4BM00234B

    Article  CAS  PubMed  Google Scholar 

  • Zhang B, Montgomery M, Chamberlain MD, Ogawa S, Korolj A, Pahnke A, Wells LA, Massé S, Kim J, Reis L, Momen A, Nunes SS, Wheeler AR, Nanthakumar K, Keller G, Sefton MV, Radisic M (2016) Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat Mater. doi:10.1038/nmat4570

    Google Scholar 

  • Zheng Y, Chen J, Craven M, Choi NW, Totorica S, Diaz-Santana A, Kermani P, Hempstead B, Fischbach-Teschl C, López JA, Stroock AD (2012) In vitro microvessels for the study of angiogenesis and thrombosis. Proc Natl Acad Sci U S A 109:9342–9347. doi:10.1073/pnas.1201240109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Sazer, D., Miller, J. (2017). Vascular Networks Within 3D Printed and Engineered Tissues. In: Ovsianikov, A., Yoo, J., Mironov, V. (eds) 3D Printing and Biofabrication. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-319-40498-1_23-1

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