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Engineering Pre-vascularized Scaffolds for Bone Regeneration

  • Chapter
Book cover Engineering Mineralized and Load Bearing Tissues

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 881))

Abstract

Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.

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References

  • Alsberg E, Kong HJ, Hirano Y, Smith MK, Albeiruti A, Mooney DJ (2003) Regulating bone formation via controlled scaffold degradation. J Dent Res 82(11):903–908

    Article  CAS  PubMed  Google Scholar 

  • Annabi N, Tamayol A, Uquillas JA, Akbari M, Bertassoni LE, Cha C et al (2014) 25th anniversary article: rational design and applications of hydrogels in regenerative medicine. Adv Mater 26(1):85–123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bae H, Puranik AS, Gauvin R, Edalat F, Carrillo-Conde B, Peppas NA et al (2012) Building vascular networks. Sci Transl Med 4(160):160ps23

    Article  PubMed Central  PubMed  Google Scholar 

  • Baranski JD, Chaturvedi RR, Stevens KR, Eyckmans J, Carvalho B, Solorzano RD et al (2013) Geometric control of vascular networks to enhance engineered tissue integration and function. Proc Natl Acad Sci U S A 110(19):7586–7591

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bergers G, Song S (2005) The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 7(4):452–464

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bertassoni LE, Cecconi M, Manoharan V, Nikkhah M, Hjortnaes J, Cristino AL et al (2014a) Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Lab Chip 14(13):2202–2211

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bertassoni LE, Cardoso JC, Manoharan V, Cristino AL, Bhise NS, Araujo WA et al (2014b) Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels. Biofabrication 6(2):024105

    Article  PubMed Central  PubMed  Google Scholar 

  • Berthod F, Germain L, Tremblay N, Auger FA (2006) Extracellular matrix deposition by fibroblasts is necessary to promote capillary-like tube formation in vitro. J Cell Physiol 207(2):491–498

    Article  CAS  PubMed  Google Scholar 

  • Bischel LL, Young EW, Mader BR, Beebe DJ (2013) Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials 34(5):1471–1477

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Black AF, Berthod F, L’Heureux N, Germain L, Auger FA (1998) In vitro reconstruction of a human capillary-like network in a tissue-engineered skin equivalent. FASEB J Off Publ Fed Am Soc Exp Biol 12(13):1331–1340

    CAS  Google Scholar 

  • Brandi ML, Collin-Osdoby P (2006) Vascular biology and the skeleton. J Bone Miner Res Off J Am Soc Bone Miner Res 21(2):183–192

    Article  CAS  Google Scholar 

  • Burkus JK, Ganey TM, Ogden JA (1993) Development of the cartilage canals and the secondary center of ossification in the distal chondroepiphysis of the prenatal human femur. Yale J Biol Med 66(3):193–202

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chen C, Hirdes D, Folch A (2003) Gray-scale photolithography using microfluidic photomasks. Proc Natl Acad Sci U S A 100(4):1499–1504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen FM, Chen R, Wang XJ, Sun HH, Wu ZF (2009) In vitro cellular responses to scaffolds containing two microencapulated growth factors. Biomaterials 30(28):5215–5224

    Article  CAS  PubMed  Google Scholar 

  • Chen YC, Lin RZ, Qi H, Yang Y, Bae H, Melero-Martin JM et al (2012) Functional human vascular network generated in photocrosslinkable gelatin methacrylate hydrogels. Adv Funct Mater 22(10):2027–2039

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cheung C (2005) The future of bone healing. Clin Podiatr Med Surg 22(4):631–641 viii

    Article  PubMed  Google Scholar 

  • Chiu LL, Montgomery M, Liang Y, Liu H, Radisic M (2012) Perfusable branching microvessel bed for vascularization of engineered tissues. Proc Natl Acad Sci U S A 109(50):E3414–E3423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clark ER, Clark LB (1939) Microscopic observations on the growth of blood capillaries in the living mammal. Dev Dyn 64(2):251–301

    Google Scholar 

  • Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol CJASN 3(Suppl 3):S131–S139

    Article  CAS  PubMed  Google Scholar 

  • Comisar WA, Kazmers NH, Mooney DJ, Linderman JJ (2007) Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: a combined computational and experimental approach. Biomaterials 28(30):4409–4417

    Article  CAS  PubMed  Google Scholar 

  • Cuchiara MP, Gould DJ, McHale MK, Dickinson ME, West JL (2012) Integration of self-assembled microvascular networks with microfabricated PEG-based hydrogels. Adv Funct Mater 22(21):4511–4518

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Curray JD (2006) Bones: structure and mechanics. Princeton University Press, Princeton, p 456

    Google Scholar 

  • Derby B (2012) Printing and prototyping of tissues and scaffolds. Science 338(6109):921–926

    Article  CAS  PubMed  Google Scholar 

  • Elbjeirami WM, West JL (2006) Angiogenesis-like activity of endothelial cells co-cultured with VEGF-producing smooth muscle cells. Tissue Eng 12(2):381–390

    Article  CAS  PubMed  Google Scholar 

  • Ennett AB, Kaigler D, Mooney DJ (2006) Temporally regulated delivery of VEGF in vitro and in vivo. J Biomed Mater Res A 79(1):176–184

    Article  PubMed  Google Scholar 

  • Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288(5791):551–556

    Article  CAS  PubMed  Google Scholar 

  • Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267(16):10931–10934

    CAS  PubMed  Google Scholar 

  • Gerber HP, Ferrara N (2000) Angiogenesis and bone growth. Trends Cardiovasc Med 10(5):223–228

    Article  CAS  PubMed  Google Scholar 

  • Goldberg VM, Stevenson S (1987) Natural history of autografts and allografts. Clin Orthop Relat Res 225:7–16

    PubMed  Google Scholar 

  • Hernandez CJ, Keaveny TM (2006) A biomechanical perspective on bone quality. Bone 39(6):1173–1181

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hu X, Zhang P, Xu Z, Chen H, Xie X (2013) GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: potential role for tissue engineering bone. J Cell Biochem 114(12):2729–2737

    Article  CAS  PubMed  Google Scholar 

  • Invernici G, Madeddu P, Emanueli C, Parati EA, Alessandri G (2008) Human fetal aorta-derived vascular progenitor cells: identification and potential application in ischemic diseases. Cytotechnology 58(1):43–47

    Article  PubMed Central  PubMed  Google Scholar 

  • Jain RK, Au P, Tam J, Duda DG, Fukumura D (2005) Engineering vascularized tissue. Nat Biotechnol 23(7):821–823

    Article  CAS  PubMed  Google Scholar 

  • Jansen JA, Vehof JW, Ruhe PQ, Kroeze-Deutman H, Kuboki Y, Takita H et al (2005) Growth factor-loaded scaffolds for bone engineering. J Control Release 101(1–3):127–136

    Article  CAS  PubMed  Google Scholar 

  • Jeon O, Song SJ, Kang SW, Putnam AJ, Kim BS (2007) Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly (L-lactic-co-glycolic acid) scaffold. Biomaterials 28(17):2763–2771

    Article  CAS  PubMed  Google Scholar 

  • Jeong JH, Chan V, Cha C, Zorlutuna P, Dyck C, Hsia KJ et al (2012) “Living” microvascular stamp for patterning of functional neovessels; orchestrated control of matrix property and geometry. Adv Mater 24(1):58–63, 1

    Article  CAS  PubMed  Google Scholar 

  • Johnell O (1997) The socioeconomic burden of fractures: today and in the 21st century. Am J Med 103(2A):20S–25S; discussion 5S–6S

    Article  CAS  PubMed  Google Scholar 

  • Kanczler JM, Oreffo RO (2008) Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater 15:100–114

    CAS  PubMed  Google Scholar 

  • Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26(27):5474–5491

    Article  CAS  PubMed  Google Scholar 

  • Kim C, Chung S, Yuchun L, Kim MC, Chan JK, Asada HH et al (2012) In vitro angiogenesis assay for the study of cell-encapsulation therapy. Lab Chip 12(16):2942–2950

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Lee H, Chung M, Jeon NL (2013) Engineering of functional, perfusable 3D microvascular networks on a chip. Lab Chip 13(8):1489–1500

    Article  CAS  PubMed  Google Scholar 

  • Kim C, Kasuya J, Jeon J, Chung S, Kamm RD (2015) A quantitative microfluidic angiogenesis screen for studying anti-angiogenic therapeutic drugs. Lab Chip 15(1):301–310

    Article  PubMed  Google Scholar 

  • Kimoto T, Hosokawa R, Kubo T, Maeda M, Sano A, Akagawa Y (1998) Continuous administration of basic fibroblast growth factor (FGF-2) accelerates bone induction on rat calvaria–an application of a new drug delivery system. J Dent Res 77(12):1965–1969

    Article  CAS  PubMed  Google Scholar 

  • Koester KJ, Ager JW 3rd, Ritchie RO (2008) The true toughness of human cortical bone measured with realistically short cracks. Nat Mater 7(8):672–677

    Article  CAS  PubMed  Google Scholar 

  • Kubota Y, Kleinman HK, Martin GR, Lawley TJ (1988) Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J Cell Biol 107(4):1589–1598

    Article  CAS  PubMed  Google Scholar 

  • Kusuma S, Shen YI, Hanjaya-Putra D, Mali P, Cheng L, Gerecht S (2013) Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix. Proc Natl Acad Sci U S A 110(31):12601–12606

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100(6):782–794

    Article  CAS  PubMed  Google Scholar 

  • Laschke MW, Vollmar B, Menger MD (2009) Inosculation: connecting the life-sustaining pipelines. Tissue Eng Part B Rev 15(4):455–465

    Article  PubMed  Google Scholar 

  • LeBlanc AJ, Krishnan L, Sullivan CJ, Williams SK, Hoying JB (2012) Microvascular repair: post-angiogenesis vascular dynamics. Microcirculation 19(8):676–695

    Article  PubMed  Google Scholar 

  • Lee VK, Kim DY, Ngo H, Lee Y, Seo L, Yoo SS et al (2014) Creating perfused functional vascular channels using 3D bio-printing technology. Biomaterials 35(28):8092–8102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leslie-Barbick JE, Moon JJ, West JL (2009) Covalently-immobilized vascular endothelial growth factor promotes endothelial cell tubulogenesis in poly (ethylene glycol) diacrylate hydrogels. J Biomater Sci Polym Ed 20(12):1763–1779

    Article  CAS  PubMed  Google Scholar 

  • Leslie-Barbick JE, Saik JE, Gould DJ, Dickinson ME, West JL (2011a) The promotion of microvasculature formation in poly (ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide. Biomaterials 32(25):5782–5789

    Article  CAS  PubMed  Google Scholar 

  • Leslie-Barbick JE, Shen C, Chen C, West JL (2011b) Micron-scale spatially patterned, covalently immobilized vascular endothelial growth factor on hydrogels accelerates endothelial tubulogenesis and increases cellular angiogenic responses. Tissue Eng Part A 17(1–2):221–229

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu Y, Lim J, Teoh SH (2013) Review: development of clinically relevant scaffolds for vascularised bone tissue engineering. Biotechnol Adv 31(5):688–705

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Chan JK, Teoh SH (2015) Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems. J Tissue Eng Regen Med 9(2):85–105

    Article  CAS  PubMed  Google Scholar 

  • Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23(1):47–55

    Article  CAS  PubMed  Google Scholar 

  • Lutolf MP, Weber FE, Schmoekel HG, Schense JC, Kohler T, Muller R et al (2003) Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat Biotechnol 21(5):513–518

    Article  CAS  PubMed  Google Scholar 

  • Mapili G, Lu Y, Chen S, Roy K (2005) Laser-layered microfabrication of spatially patterned functionalized tissue-engineering scaffolds. J Biomed Mater Res B Appl Biomater 75(2):414–424

    Article  PubMed  Google Scholar 

  • Mata A, Boehm C, Fleischman AJ, Muschler G, Roy S (2002) Analysis of connective tissue progenitor cell behavior on polydimethylsiloxane smooth and channel micro-textures. Biomed Microdevices 4(4):267–275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mehta M, Schmidt-Bleek K, Duda GN, Mooney DJ (2012) Biomaterial delivery of morphogens to mimic the natural healing cascade in bone. Adv Drug Deliv Rev 64(12):1257–1276

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mercado-Pagan AE, Stahl AM, Shanjani Y, Yang Y (2015) Vascularization in bone tissue engineering constructs. Ann Biomed Eng 43(3):718–729

    Article  PubMed  Google Scholar 

  • Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM et al (2012) Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater 11(9):768–774

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Montesano R, Orci L, Vassalli P (1983) In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. J Cell Biol 97(5 Pt 1):1648–1652

    Article  CAS  PubMed  Google Scholar 

  • Nguyen LH, Annabi N, Nikkhah M, Bae H, Binan L, Park S et al (2012) Vascularized bone tissue engineering: approaches for potential improvement. Tissue Eng Part B Rev 18(5):363–382

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nguyen DH, Stapleton SC, Yang MT, Cha SS, Choi CK, Galie PA et al (2013) Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. Proc Natl Acad Sci U S A 110(17):6712–6717

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nikkhah M, Eshak N, Zorlutuna P, Annabi N, Castello M, Kim K et al (2012) Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials 33(35):9009–9018

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Obregon F, Vaquette C, Ivanovski S, Hutmacher DW, Bertassoni LE (2015) Three dimensional bioprinting for regenerative dentistry and craniofacial tissue engineering. J Dental Res 94(9, suppl no. 2):1435S–152S

    Google Scholar 

  • Oest ME, Dupont KM, Kong HJ, Mooney DJ, Guldberg RE (2007) Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects. J Orthop Res 25(7):941–950

    Article  CAS  PubMed  Google Scholar 

  • Oldham JB, Lu L, Zhu X, Porter BD, Hefferan TE, Larson DR et al (2000) Biological activity of rhBMP-2 released from PLGA microspheres. J Biomech Eng 122(3):289–292

    Article  CAS  PubMed  Google Scholar 

  • Patel ZS, Young S, Tabata Y, Jansen JA, Wong ME, Mikos AG (2008) Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone 43(5):931–940

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Peters MC, Polverini PJ, Mooney DJ (2002) Engineering vascular networks in porous polymer matrices. J Biomed Mater Res 60(4):668–678

    Article  CAS  PubMed  Google Scholar 

  • Portal-Nunez S, Lozano D, Esbrit P (2012) Role of angiogenesis on bone formation. Histol Histopathol 27(5):559–566

    CAS  PubMed  Google Scholar 

  • Praemer A, Furner S, Rice D (1992) Musculoskeletal conditions in the United States. American Academy of Orthopaedic Surgeons, Park Ridge

    Google Scholar 

  • Qin D, Xia Y, Whitesides GM (2010) Soft lithography for micro- and nanoscale patterning. Nat Protoc 5(3):491–502

    Article  CAS  PubMed  Google Scholar 

  • Radisic M, Yang L, Boublik J, Cohen RJ, Langer R, Freed LE et al (2004) Medium perfusion enables engineering of compact and contractile cardiac tissue. Am J Physiol Heart Circ Physiol 286(2):H507–H516

    Article  CAS  PubMed  Google Scholar 

  • Raghavan S, Nelson CM, Baranski JD, Lim E, Chen CS (2010) Geometrically controlled endothelial tubulogenesis in micropatterned gels. Tissue Eng Part A 16(7):2255–2263

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ratner BD (1996) The engineering of biomaterials exhibiting recognition and specificity. J Mol Recog JMR 9(5–6):617–625

    Article  CAS  Google Scholar 

  • Real C, Caiado F, Dias S (2008) Endothelial progenitors in vascular repair and angiogenesis: how many are needed and what to do? Cardiovasc Hematol Disord Drug Targets 8(3):185–193

    Article  CAS  PubMed  Google Scholar 

  • Reports of the Surgeon General (2004) Bone health and osteoporosis: a report of the surgeon general, Rockville

    Google Scholar 

  • Ribatti D, Crivellato E (2012) “Sprouting angiogenesis”, a reappraisal. Dev Biol 372(2):157–165

    Article  CAS  PubMed  Google Scholar 

  • Richardson TP, Peters MC, Ennett AB, Mooney DJ (2001) Polymeric system for dual growth factor delivery. Nat Biotechnol 19(11):1029–1034

    Article  CAS  PubMed  Google Scholar 

  • Risau W (1997) Mechanisms of angiogenesis. Nature 386(6626):671–674

    Article  CAS  PubMed  Google Scholar 

  • Rodan GA, Raisz LG, Bilezikian JP (1996) Principles of bone biology. Academic, San Diego, pp 3–24

    Google Scholar 

  • Rowley JA, Madlambayan G, Mooney DJ (1999) Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20(1):45–53

    Article  CAS  PubMed  Google Scholar 

  • Santo VE, Frias AM, Carida M, Cancedda R, Gomes ME, Mano JF et al (2009) Carrageenan-based hydrogels for the controlled delivery of PDGF-BB in bone tissue engineering applications. Biomacromolecules 10(6):1392–1401

    Article  PubMed  Google Scholar 

  • Sasagawa T, Shimizu T, Sekiya S, Haraguchi Y, Yamato M, Sawa Y et al (2010) Design of prevascularized three-dimensional cell-dense tissues using a cell sheet stacking manipulation technology. Biomaterials 31(7):1646–1654

    Article  CAS  PubMed  Google Scholar 

  • Sato N, Sawasaki Y, Senoo A, Fuse Y, Hirano Y, Goto T (1987) Development of capillary networks from rat microvascular fragments in vitro: the role of myofibroblastic cells. Microvasc Res 33(2):194–210

    Article  CAS  PubMed  Google Scholar 

  • Schmid J, Wallkamm B, Hammerle CH, Gogolewski S, Lang NP (1997) The significance of angiogenesis in guided bone regeneration. A case report of a rabbit experiment. Clin Oral Implants Res 8(3):244–248

    Article  CAS  PubMed  Google Scholar 

  • Simmons CA, Alsberg E, Hsiong S, Kim WJ, Mooney DJ (2004) Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone 35(2):562–569

    Article  CAS  PubMed  Google Scholar 

  • Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA (2009) Hydrogels in regenerative medicine. Adv Mater 21(32–33):3307–3329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Street J, Bao M, de Guzman L, Bunting S, Peale FV Jr, Ferrara N et al (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A 99(15):9656–9661

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Supp DM, Wilson-Landy K, Boyce ST (2002) Human dermal microvascular endothelial cells form vascular analogs in cultured skin substitutes after grafting to athymic mice. FASEB J 16(8):797–804

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tasoglu S, Demirci U (2013) Bioprinting for stem cell research. Trends Biotechnol 31(1):10–19

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Torisawa YS, Spina CS, Mammoto T, Mammoto A, Weaver JC, Tat T et al (2014) Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat Methods 11(6):663–669

    Article  CAS  PubMed  Google Scholar 

  • Tsigkou O, Pomerantseva I, Spencer JA, Redondo PA, Hart AR, O’Doherty E et al (2010) Engineered vascularized bone grafts. Proc Natl Acad Sci U S A 107(8):3311–3316

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vailhe B, Vittet D, Feige JJ (2001) In vitro models of vasculogenesis and angiogenesis. Lab Investig J Tech Methods Pathol 81(4):439–452

    Article  CAS  Google Scholar 

  • Vernon RB, Sage EH (1999) A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices. Microvasc Res 57(2):118–133

    Article  CAS  PubMed  Google Scholar 

  • Wang DS, Miura M, Demura H, Sato K (1997) Anabolic effects of 1,25-dihydroxyvitamin D3 on osteoblasts are enhanced by vascular endothelial growth factor produced by osteoblasts and by growth factors produced by endothelial cells. Endocrinology 138(7):2953–2962

    CAS  PubMed  Google Scholar 

  • Wegst UG, Bai H, Saiz E, Tomsia AP, Ritchie RO (2015) Bioinspired structural materials. Nat Mater 14(1):23–36

    Article  CAS  PubMed  Google Scholar 

  • Woolf AD, Pfleger B (2003) Bulletin of the world health organization. Contract No.: 9

    Google Scholar 

  • Wray LS, Tsioris K, Gi ES, Omenetto FG, Kaplan DL (2013) Slowly degradable porous silk microfabricated scaffolds for vascularized tissue formation. Adv Funct Mater 23(27):3404–3412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yilgor P, Hasirci N, Hasirci V (2010) Sequential BMP-2/BMP-7 delivery from polyester nanocapsules. J Biomed Mater Res A 93(2):528–536

    CAS  PubMed  Google Scholar 

  • Zhang R, Gao Z, Geng W, Yan X, Chen F, Liu Y (2012) Engineering vascularized bone graft with osteogenic and angiogenic lineage differentiated bone marrow mesenchymal stem cells. Artif Organs 36(12):1036–1046

    Article  CAS  PubMed  Google Scholar 

  • Zheng Y, Chen J, Craven M, Choi NW, Totorica S, Diaz-Santana A et al (2012) In vitro microvessels for the study of angiogenesis and thrombosis. Proc Natl Acad Sci U S A 109(24):9342–9347

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zimmermann EA, Schaible E, Bale H, Barth HD, Tang SY, Reichert P et al (2011) Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales. Proc Natl Acad Sci U S A 108(35):14416–14421

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, Sydney, NSW, Australia

    Giada D. G. Barabaschi & Qing Li

  2. Bioengineering Laboratory, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia

    Giada D. G. Barabaschi & Luiz E. Bertassoni DDS, Ph.D.

  3. Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, USA

    Vijayan Manoharan

  4. Center for Regenerative Medicine, Oregon Health and Science University, Portland, OR, USA

    Luiz E. Bertassoni DDS, Ph.D.

  5. Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, Oregon Health and Science University, Portland, OR, USA

    Luiz E. Bertassoni DDS, Ph.D.

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  1. Giada D. G. Barabaschi
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  2. Vijayan Manoharan
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  3. Qing Li
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  4. Luiz E. Bertassoni DDS, Ph.D.
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Correspondence to Luiz E. Bertassoni DDS, Ph.D. .

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Editors and Affiliations

  1. Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon, USA

    Luiz E. Bertassoni

  2. Department of Biomaterials and Biomimetics, New York University, New York, New York, USA

    Paulo G. Coelho

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Barabaschi, G.D.G., Manoharan, V., Li, Q., Bertassoni, L.E. (2015). Engineering Pre-vascularized Scaffolds for Bone Regeneration. In: Bertassoni, L., Coelho, P. (eds) Engineering Mineralized and Load Bearing Tissues. Advances in Experimental Medicine and Biology, vol 881. Springer, Cham. https://doi.org/10.1007/978-3-319-22345-2_5

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