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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
King KR, Wang CCJ, Kaazempur-Mofrad MR, Vacanti JP, Borenstein JT (2004) Biodegradable microfluids. Adv Mater 16:2007–2012. doi:10.1002/adma.200306522
Kinstlinger IS, Miller J (2016) 3D-printed fluidic networks as vasculature for engineered tissue. Lab Chip 16:2025–2043. doi:10.1039/C6LC00193A
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
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
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
Langer R, Folkman J (1976) Polymers for the sustained release of proteins and other macromolecules. Nature 263:797–800
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
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
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
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
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
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
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
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
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
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
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
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
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
Ratner B, Hoffman A, Schoen F, Lemons J (2004) Biomaterials science: an introduction to materials in medicine, 2nd edn. Academic, Cambridge
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
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
Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–684
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
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
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
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
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
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
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
Vacanti CA (2006) The history of tissue engineering. J Cell Mol Med 10:569–576. doi:10.1111/j.1582-4934.2006.tb00421.x
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
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
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
Wu W, Deconinck A, Lewis JA (2011) Omnidirectional printing of 3D microvascular networks. Adv Mater 23:178–183. doi:10.1002/adma.201004625
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
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
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
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
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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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