Skip to main content
SpringerLink
Log in

Microengineered platforms for co-cultured mesenchymal stem cells towards vascularized bone tissue engineering

  • Review Article
  • Tissue Engineering
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Bone defects are common disease requiring thorough treatments since the bone is a complex vascularized tissue that is composed of multiple cell types embedded within an intricate extracellular matrix (ECM). For past decades, tissue engineering using cells, proteins, and scaffolds has been suggested as one of the promising approaches for effective bone regeneration. Recently, many researchers have been interested in designing effective platform for tissue regeneration by orchestrating factors involved in microenvironment around tissues. Among factors affecting bone formation, vascularization during bone development and after minor insults via endochondral and intramembranous ossification is especially critical for the long-term support for functional bone. In order to create vascularized bone constructs, the interactions between human mesenchymal stem cells (MSCs) and endothelial cells (ECs) have been investigated using both direct and indirect co-culture studies. Recently, various culture methods including micropatterning techniques, three dimensional scaffolds, and microfluidics have been developed to create micro-engineered platforms that mimic the nature of vascularized bone formation, leading to the creation of functional bone structures. This review focuses on MSCs co-cultured with endothelial cells and microengineered platforms to determine the underlying interplay between co-cultured MSCs and vascularized bone constructs, which is ultimately necessary for adequate regeneration of bone defects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sharma B, Elisseeff JH. Engineering structurally organized cartilage and bone tissues. Ann Biomed Eng 2004;32:148–159.

    Article  PubMed  Google Scholar 

  2. Laurencin CT, Ambrosio AM, Borden MD, Cooper JA Jr. Tissue engineering:orthopedic applications. Annu Rev Biomed Eng 1999;1:19–46.

    Article  CAS  PubMed  Google Scholar 

  3. Santos MI, Reis RL. Vascularization in bone tissue engineering:physiology, current strategies, major hurdles and future challenges. Macromol Biosci 2010;10:12–27.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv Drug Deliv Rev 2012;64:1292–1309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Klenke FM, Liu Y, Yuan H, Hunziker EB, Siebenrock KA, Hofstetter W. Impact of pore size on the vascularization and osseointegration of ceramic bone substitutes in vivo. J Biomed Mater Res A 2008;85:777–786.

    Article  PubMed  Google Scholar 

  7. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 1999;103:159–165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Koike N, Fukumura D, Gralla O, Au P, Schechner JS, Jain RK. Tissue engineering:creation of long-lasting blood vessels. Nature 2004;428:138–139.

    Article  CAS  PubMed  Google Scholar 

  9. Saran U, Gemini Piperni S, Chatterjee S. Role of angiogenesis in bone repair. Arch Biochem Biophys 2014;561:109–117.

    Article  CAS  PubMed  Google Scholar 

  10. Marie PJ, Fromigué O. Osteogenic differentiation of human marrow-derived mesenchymal stem cells. Regen Med 2006;1:539–548.

    Article  CAS  PubMed  Google Scholar 

  11. Phinney DG, Prockop DJ. Concise review:mesenchymal stem/multipotent stromal cells:the state of transdifferentiation and modes of tissue repair—current views. Stem Cells 2007;25:2896–2902.

    Article  PubMed  Google Scholar 

  12. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147.

    Article  CAS  PubMed  Google Scholar 

  13. McFadden TM, Duffy GP, Allen AB, Stevens HY, Schwarzmaier SM, Plesnila N, et al. The delayed addition of human mesenchymal stem cells to pre-formed endothelial cell networks results in functional vascularization of a collagen-glycosaminoglycan scaffold in vivo. Acta Biomater 2013;9303–9316.

    Google Scholar 

  14. Dimitriou R, Tsiridis E, Giannoudis PV. Current concepts of molecular aspects of bone healing. Injury 2005;36:1392–1404.

    Article  PubMed  Google Scholar 

  15. Oswald J, Boxberger S, Jørgensen B, Feldmann S, Ehninger G, Bornhäuser M, et al. Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 2004;22:377–384.

    Article  PubMed  Google Scholar 

  16. Au P, Tam J, Fukumura D, Jain RK. Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood 2008;111:4551–4558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kirkpatrick CJ, Fuchs S, Unger RE. Co-culture systems for vascularization—learning from nature. Adv Drug Deliv Rev 2011;63:291–299.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Weatherholt AM, Fuchs RK, Warden SJ. Specialized connective tissue:bone, the structural framework of the upper extremity. J Hand Ther 2012;25:123–131;quiz132.

    Article  PubMed  Google Scholar 

  20. Meghji S. Bone remodelling. Br Dent J 1992;172:235–242.

    Article  CAS  PubMed  Google Scholar 

  21. Rey C, Combes C, Drouet C, Glimcher MJ. Bone mineral:update on chemical composition and structure. Osteoporos Int 2009;20:1013–1021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Robinson RA. Bone tissue:composition and function. Johns Hopkins Med J 1979;145:10–24.

    CAS  PubMed  Google Scholar 

  23. Eastoe JE. The chemical composition of bone and tooth. Adv Fluorine Res 1965;21:5–17.

    CAS  PubMed  Google Scholar 

  24. Ashman RF, Buckwalter JA, Devane P, Dobbs MB, Ferguson PJ, Flatow EL, et al. Turek’s Orthopaedics:Principles and Their Application. 6th ed. Iowa City:Lippincott Williams and Wilkins;2005.

    Google Scholar 

  25. Yang L, Perez-Amodio S, Barrère- de Groot FY, Everts V, van Blitterswijk CA, Habibovic P. The effects of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts. Biomaterials 2010;31:2976–2989.

    Article  CAS  PubMed  Google Scholar 

  26. Fung YC. Biomechanics:Mechanical Properties of Living Tissues. 2nd ed. New York:Springer-Verlag;1993.

    Book  Google Scholar 

  27. Alford AI, Kozloff KM, Hankenson KD. Extracellular matrix networks in bone remodeling. Int J Biochem Cell Biol 2015;65:20–31.

    Article  CAS  PubMed  Google Scholar 

  28. Nijweide PJ, Burger EH, Feyen JH. Cells of bone:proliferation, differentiation, and hormonal regulation. Physiol Rev 1986;66:855–886.

    CAS  PubMed  Google Scholar 

  29. Heino TJ, Kurata K, Higaki H, Väänänen HK. Evidence for the role of osteocytes in the initiation of targeted remodeling. Technol Health Care 2009;17:49–56.

    PubMed  Google Scholar 

  30. Vrahnas C, Sims NA. EphrinB2 signalling in osteoblast differentiation, bone formation and endochondral ossification. Curr Mol Bio Rep 2015;1:148–156.

    Article  Google Scholar 

  31. Ehninger A, Trumpp A. The bone marrow stem cell niche grows up:mesenchymal stem cells and macrophages move in. J Exp Med 2011;208:421–428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yin T, Li L. The stem cell niches in bone. J Clin Invest 2006;116:1195–1201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Caplan AI. Why are MSCs therapeutic? New data:new insight. J Pathol 2009;217:318–324.

    Article  CAS  PubMed  Google Scholar 

  34. Müller-Sieburg CE, Cho RH, Thoman M, Adkins B, Sieburg HB. Deterministic regulation of hematopoietic stem cell self-renewal and differentiation. Blood 2002;100:1302–1309.

    PubMed  Google Scholar 

  35. Marieb EN, Hoehn k. Human anatomy and physiology. 7th ed. San Francisco, CA: Pearson Benjamin Cummings;2007. xxvii. 1159. A1-I51 p.

    Google Scholar 

  36. Mackie EJ, Tatarczuch L, Mirams M. The skeleton:a multi-functional complex organ:the growth plate chondrocyte and endochondral ossification. J Endocrinol 2011;211:109–121.

    Article  CAS  PubMed  Google Scholar 

  37. Thompson Z, Miclau T, Hu D, Helms JA. A model for intramembranous ossification during fracture healing. J Orthop Res 2002;20:1091–1098.

    Article  CAS  PubMed  Google Scholar 

  38. Ortega N, Behonick DJ, Werb Z. Matrix remodeling during endochondral ossification. Trends Cell Biol 2004;14:86–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schindeler A, McDonald MM, Bokko P, Little DG. Bone remodeling during fracture repair:the cellular picture. Semin Cell Dev Biol 2008;19:459–466.

    Article  CAS  PubMed  Google Scholar 

  40. Streeten EA, Brandi ML. Biology of bone endothelial cells. Bone Miner 1990;10:85–94.

    Article  CAS  PubMed  Google Scholar 

  41. Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials 2005;26:4139–4147.

    Article  CAS  PubMed  Google Scholar 

  42. Lu Y, Lekszycki T. Modeling of an initial stage of bone fracture healing. Continuum Mech Thermodyn 2015;27:851–859.

    Article  Google Scholar 

  43. Cruess RL, Dumont J. Fracture healing. Can J Surg 1975;18:403–413.

    CAS  PubMed  Google Scholar 

  44. Ketenjian AY, Jafri AM, Arsenis C. Studies on the mechanism of callus cartilage differentiation and calcification during fracture healing. Orthop Clin North Am 1978;9:43–65.

    CAS  PubMed  Google Scholar 

  45. Tsunoda M, Mizuno K, Matsubara T. The osteogenic potential of fracture hematoma and its mechanism on bone formation—through fracture hematoma culture and transplantation of freeze-dried hematoma. Kobe J Med Sci 1993;39:35–50.

    CAS  PubMed  Google Scholar 

  46. Macmahon P, Eustace SJ. General principles. Semin Musculoskelet Radiol 2006;10:243–248.

    Article  PubMed  Google Scholar 

  47. Sfeir C, Ho L, Doll BA, Azari K, Hollinger JO. Fracture Repair. In:Lieberman JR, Friedlander GE, editors. Bone Regeneration and Repair:Biology and Clinical Applications. Totowa, NJ: Humana Press Inc.;2005.

    Google Scholar 

  48. Singh MAF. Exercise and bone health. Nutrition and Bone Health. New York, NY: Springer;2015. p. 505–542.

    Google Scholar 

  49. Cowin SC. Wolff’s law of trabecular architecture at remodeling equilibrium. J Biomech Eng 1986;108:83–88.

    Article  CAS  PubMed  Google Scholar 

  50. Greer RB 3rd. Wolff’s Law. Orthop Rev 1993;22:1087–1088.

    PubMed  Google Scholar 

  51. Battiston KG, Cheung JW, Jain D, Santerre JP. Biomaterials in co-culture systems:towards optimizing tissue integration and cell signaling within scaffolds. Biomaterials 2014;35:4465–4476.

    Article  CAS  PubMed  Google Scholar 

  52. Jin GZ, Han CM, Kim HW. In vitro co-culture strategies to prevascularization for bone regeneration:a brief update. Tissue Eng Regen Med 2015;12:69–79.

    Article  CAS  Google Scholar 

  53. Suh JD, Lim KT, Jin H, Kim J, Choung PH, Chung JH. Effects of co-culture of dental pulp stem cells and periodontal ligament stem cells on assembled dual disc scaffolds. Tissue Eng Regen Med 2014;11:47–58.

    Article  CAS  Google Scholar 

  54. Lawrence TS, Beers WH, Gilula NB. Transmission of hormonal stimulation by cell-to-cell communication. Nature 1978;272:501–506.

    Article  CAS  PubMed  Google Scholar 

  55. El-Sabban ME, Sfeir AJ, Daher MH, Kalaany NY, Bassam RA, Talhouk RS. ECM-induced gap junctional communication enhances mammary epithelial cell differentiation. J Cell Sci 2003;116:3531–3541.

    Article  CAS  PubMed  Google Scholar 

  56. Sinclair SS, Burg KJ. Effect of osteoclast co-culture on the differentiation of human mesenchymal stem cells grown on bone graft granules. J Biomater Sci Polym Ed 2011;22:789–808.

    Article  CAS  PubMed  Google Scholar 

  57. Joensuu K, Uusitalo L, Alm JJ, Aro HT, Hentunen TA, Heino TJ. Enhanced osteoblastic differentiation and bone formation in co-culture of human bone marrow mesenchymal stromal cells and peripheral blood mononuclear cells with exogenous VEGF. Orthop Traumatol Surg Res 2015;101:381–386.

    Article  CAS  PubMed  Google Scholar 

  58. Kolbe M, Xiang Z, Dohle E, Tonak M, Kirkpatrick CJ, Fuchs S. Paracrine effects influenced by cell culture medium and consequences on microvessel-like structures in cocultures of mesenchymal stem cells and outgrowth endothelial cells. Tissue Eng Part A 2011;17:2199–2212.

    Article  CAS  PubMed  Google Scholar 

  59. Ern C, Krump-Konvalinkova V, Docheva D, Schindler S, Rossmann O, Böcker W, et al. Interactions of human endothelial and multipotent mesenchymal stem cells in cocultures. Open Biomed Eng J 2010;4:190–198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pedersen TO, Blois AL, Xue Y, Xing Z, Cottler-Fox M, Fristad I, et al. Osteogenic stimulatory conditions enhance growth and maturation of endothelial cell microvascular networks in culture with mesenchymal stem cells. J Tissue Eng 2012;3:2041731412443236.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Paschos NK, Brown WE, Eswaramoorthy R, Hu JC, Athanasiou KA. Advances in tissue engineering through stem cell-based co-culture. J Tissue Eng Regen Med 2015;9:488–503.

    Article  CAS  PubMed  Google Scholar 

  62. Melchiorri AJ, Nguyen BN, Fisher JP. Mesenchymal stem cells:roles and relationships in vascularization. Tissue Eng Part B Rev 2014;20:218–228.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Ball SG, Shuttleworth AC, Kielty CM. Direct cell contact influences bone marrow mesenchymal stem cell fate. Int J Biochem Cell Biol 2004;36:714–727.

    Article  CAS  PubMed  Google Scholar 

  64. Rouwkema J, de Boer J, Van Blitterswijk CA. Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct. Tissue Eng 2006;12:2685–2693.

    Article  CAS  PubMed  Google Scholar 

  65. Saleh FA, Whyte M, Genever PG. Effects of endothelial cells on human mesenchymal stem cell activity in a three-dimensional in vitro model. Eur Cell Mater 2011;22:242–257.

    CAS  PubMed  Google Scholar 

  66. Fu WL, Xiang Z, Huang FG, Gu ZP, Yu XX, Cen SQ, et al. Coculture of peripheral blood-derived mesenchymal stem cells and endothelial progenitor cells on strontium-doped calcium polyphosphate scaffolds to generate vascularized engineered bone. Tissue Eng Part A 2015;21:948–959.

    Article  CAS  PubMed  Google Scholar 

  67. Goers L, Freemont P, Polizzi KM. Co-culture systems and technologies:taking synthetic biology to the next level. J R Soc Interface 2014;11.

    Google Scholar 

  68. Fuchs S, Ghanaati S, Orth C, Barbeck M, Kolbe M, Hofmann A, et al. Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds. Biomaterials 2009;30:526–534.

    Article  CAS  PubMed  Google Scholar 

  69. Santos MI, Unger RE, Sousa RA, Reis RL, Kirkpatrick CJ. Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone-starch scaffold and the in vitro development of vascularization. Biomaterials 2009;30:4407–4415.

    Article  CAS  PubMed  Google Scholar 

  70. Unger RE, Sartoris A, Peters K, Motta A, Migliaresi C, Kunkel M, et al. Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials. Biomaterials 2007;28:3965–3976.

    Article  CAS  PubMed  Google Scholar 

  71. Usami K, Mizuno H, Okada K, Narita Y, Aoki M, Kondo T, et al. Composite implantation of mesenchymal stem cells with endothelial progenitor cells enhances tissue-engineered bone formation. J Biomed Mater Res A 2009;90:730–741.

    Article  PubMed  Google Scholar 

  72. Correia C, Grayson WL, Park M, Hutton D, Zhou B, Guo XE, et al. In vitro model of vascularized bone:synergizing vascular development and osteogenesis. PLoS One 2011;6:e28352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Peng R, Yao X, Cao B, Tang J, Ding J. The effect of culture conditions on the adipogenic and osteogenic inductions of mesenchymal stem cells on micropatterned surfaces. Biomaterials 2012;33:6008–6019.

    Article  CAS  PubMed  Google Scholar 

  74. Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Micropatterned surfaces for control of cell shape, position, and function. Biotechnol Prog 1998;14:356–363.

    Article  CAS  PubMed  Google Scholar 

  75. Kim S, Kim BS. Control of adult stem cell behavior with biomaterials. Tissue Eng Regen Med 2014;11:423–430.

    Article  CAS  Google Scholar 

  76. Nakanishi J, Takarada T, Yamaguchi K, Maeda M. Recent advances in cell micropatterning techniques for bioanalytical and biomedical sciences. Anal Sci 2008;24:67–72.

    Article  CAS  PubMed  Google Scholar 

  77. Tang MD, Golden AP, Tien J. Molding of three-dimensional microstructures of gels. J Am Chem Soc 2003;125:12988–12989.

    Article  CAS  PubMed  Google Scholar 

  78. Javaherian S, O’Donnell KA, McGuigan AP. A fast and accessible methodology for micro-patterning cells on standard culture substrates using ParafilmTM inserts. PLoS One 2011;6:e20909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Javaherian S, Li KJ, McGuigan AP. A simple and rapid method for generating patterned co-cultures with stable interfaces. Biotechniques 2013;55:21–26.

    Article  CAS  PubMed  Google Scholar 

  80. Khetan S, Burdick JA. Patterning hydrogels in three dimensions towards controlling cellular interactions. Soft Matter 2011;7:830–838.

    Article  CAS  Google Scholar 

  81. Hasan A, Paul A, Vrana NE, Zhao X, Memic A, Hwang YS, et al. Microfluidic techniques for development of 3D vascularized tissue. Biomaterials 2014;35:7308–7325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ji D, Jiang L, Jiang L, Fu X, Dong H, Yu J, et al. A novel method for photolithographic polymer shadow masking:toward high-resolution high-performance top-contact organic field effect transistors. Chem Commun (Camb) 2014;50:8328–8330.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 2004;6:483–495.

    Article  CAS  PubMed  Google Scholar 

  85. Kim J, Kim HN, Lim KT, Kim Y, Pandey S, Garg P, et al. Synergistic effects of nanotopography and co-culture with endothelial cells on osteogenesis of mesenchymal stem cells. Biomaterials 2013;34:7257–7268.

    Article  CAS  PubMed  Google Scholar 

  86. Trkov S, Eng G, Di Liddo R, Parnigotto PP, Vunjak-Novakovic G. Micropatterned three-dimensional hydrogel system to study human endothelial-mesenchymal stem cell interactions. J Tissue Eng Regen Med 2010;4:205–215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Tourovskaia A, Figueroa-Masot X, Folch A. Long-term micropatterned cell cultures in heterogeneous microfluidic environments. Conf Proc IEEE Eng Med Biol Soc 2004;4:2675–2678.

    PubMed  Google Scholar 

  88. Abbott RD, Kaplan DL. Strategies for improving the physiological relevance of human engineered tissues. Trends Biotechnol 2015;33:401–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Riehl BD, Lim JY. Macro and microfluidic flows for skeletal regenerative medicine. Cells 2012;1:1225–1245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Andersson H, van den Berg A. Microfabrication and microfluidics for tissue engineering:state of the art and future opportunities. Lab Chip 2004;4:98–103.

    Article  CAS  PubMed  Google Scholar 

  91. Hasani-Sadrabadi MM, Hajrezaei SP, Emami SH, Bahlakeh G, Daneshmandi L, Dashtimoghadam E, et al. Enhanced osteogenic differentiation of stem cells via microfluidics synthesized nanoparticles. Nanomedicine 2015;11:1809–1819

    CAS  PubMed  Google Scholar 

  92. Kirkpatrick CJ, Peters K, Hermanns MI, Bittinger F, Krump-Konvalinkova V, Fuchs S, et al. In vitro methodologies to evaluate biocompatibility:status quo and perspective. ITBM-RBM 2005;26:192–199.

    Article  Google Scholar 

  93. Yim EK, Wan AC, Le Visage C, Liao IC, Leong KW. Proliferation and differentiation of human mesenchymal stem cell encapsulated in polyelectrolyte complexation fibrous scaffold. Biomaterials 2006;27:6111–6122.

    Article  CAS  PubMed  Google Scholar 

  94. Sudo R, Chung S, Zervantonakis IK, Vickerman V, Toshimitsu Y, Griffith LG, et al. Transport-mediated angiogenesis in 3D epithelial coculture. FASEB J 2009;23:2155–2164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Shi X, Chen S, Zhao Y, Lai C, Wu H. Enhanced osteogenesis by a biomimic pseudo-periosteum-involved tissue engineering strategy. Adv Healthc Mater 2013;2:1229–1235.

    Article  CAS  PubMed  Google Scholar 

  96. Duttenhoefer F, Lara de Freitas R, Meury T, Loibl M, Benneker LM, Richards RG, et al. 3D scaffolds co-seeded with human endothelial progenitor and mesenchymal stem cells:evidence of prevascularisation within 7 days. Eur Cell Mater 2013;26:49–64.

    CAS  PubMed  Google Scholar 

  97. Bonzani IC, George JH, Stevens MM. Novel materials for bone and cartilage regeneration. Curr Opin Chem Biol 2006;10:568–575

    Article  CAS  PubMed  Google Scholar 

  98. Marieb EN, Wilhelm PB, Mallatt JB. Human Anatomy. San Francisco, CA: Pearson Benjamin Cummings;2005

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Korea

    Hyeryeon Park, Minhee Sung, Dokyun Na & Hansoo Park

  2. Department of Biomedical Engineering, University of Alabama School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Dong-Jin Lim

  3. Department of Biomedical Science, CHA University, Seongnam, Korea

    Soo-Hong Lee

Authors
  1. Hyeryeon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dong-Jin Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minhee Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Soo-Hong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dokyun Na
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hansoo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dokyun Na or Hansoo Park.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, H., Lim, DJ., Sung, M. et al. Microengineered platforms for co-cultured mesenchymal stem cells towards vascularized bone tissue engineering. Tissue Eng Regen Med 13, 465–474 (2016). https://doi.org/10.1007/s13770-016-9080-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-016-9080-7

Key Words

Search

Navigation