Tissue Engineering and Regenerative Medicine

, Volume 14, Issue 1, pp 1–14 | Cite as

Artificial Bone via Bone Tissue Engineering: Current Scenario and Challenges

  • Shivaji Kashte
  • Amit Kumar Jaiswal
  • Sachin Kadam
Review Article


Bone provides mechanical support, and flexibility to the body as a structural frame work along with mineral storage, homeostasis, and blood pH regulation. The repair and/or replacement of injured or defective bone with healthy bone or bone substitute is a critical problem in orthopedic treatment. Recent advances in tissue engineering have shown promising results in developing bone material capable of substituting the conventional autogenic or allogenic bone transplants. In the present review, we have discussed natural and synthetic scaffold materials such as metal and metal alloys, ceramics, polymers, etc. which are widely being used along with their cellular counterparts such as stem cells in bone tissue engineering with their pros and cons.


Bone Bone tissue engineering Scaffolds Growth factors Regenerative medicine 



Author would like to acknowledge University Grant Commission (UGC), Government of India, New Delhi for doctoral fellowship to Mr. Shivaji Kashte.

Compliance with ethical standards

Conflicts of interest

Authors have no potential conflicts of interest.

Ethical Statement

There are no animal experiments carried out for this article.


  1. 1.
    Sowjanya JA, Singh J, Mohita T, Sarvanan S, Moorthi A, Srinivasan N, et al. Biocomposite scaffolds containing chitosan/alginate/nano-silica for bone tissue engineering. Colloids Surf B Biointerfaces. 2013;109:294–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Rho JY, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys. 1998;20:92–102.PubMedCrossRefGoogle Scholar
  3. 3.
    Venkatesan J, Bhatnagar I, Kim S-K. Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering. Mar Drugs. 2014;12:300–16.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Fröhlich M, Grayson WL, Marolt D, Gimble JM, Kregar-Velikonja N, Vunjak-Novakovic G. Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng Part A. 2010;16:179–89.PubMedCrossRefGoogle Scholar
  5. 5.
    Oryan A, Alidadi S, Moshiri A, Maffulli N. Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res. 2014;9:18.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Deng M, James R, Laurencin CT, Kumbar SG. Nanostructured polymeric scaffolds for orthopaedic regenerative engineering. IEEE Trans Nanobiosci. 2012;11:3–14.CrossRefGoogle Scholar
  7. 7.
    Initial Evaluation and Management of Maxillofacial Injuries: Overview, Clinical Presentation and Approach for Patients with Facial Trauma, Relevant Anatomy and Contraindications. (Accessed 9 Dec 2015).
  8. 8.
    Jimi E, Hirata S, Osawa K, Terashita M, Kitamura C, Fukushima H. The current and future therapies of bone regeneration to repair bone defects. Int J Dent. 2012;2012:1–7.CrossRefGoogle Scholar
  9. 9.
    Smrke D, Rozman P, Borut GM. Treatment of bone defects-allogenic platelet gel and autologous bone technique. In: Andrades JA, editor. Regenerative Medicine and Tissue Engineering. InTech, 2013. doi: 10.5772/55987.
  10. 10.
    Gamble M, Pope J. Musculoskeletal complications of systemic lupus erythematosus: risk factors and prevalence for avascular necrosis and osteoporosis. J Rheumatol. 2015;42:1341–2.Google Scholar
  11. 11.
    Kenley R, Yim K, Abrams J, Ron E. Biotechnology and bone graft substitutes. Pharm Res. 1993;10:1393–401.PubMedCrossRefGoogle Scholar
  12. 12.
    Euler SA, Hengg C, Wambacher M, Spiegl UJ, Kralinger F. Allogenic bone grafting for augmentation in two-part proximal humeral fracture fixation in a high-risk patient population. Arch Orthop Trauma Surg. 2015;135:79–87.PubMedCrossRefGoogle Scholar
  13. 13.
    Xia Z, Yu X, Jiang X, Brody HD, Rowe DW, Wei M. Fabrication and characterization of biomimetic collagen-apatite scaffolds with tunable structures for bone tissue engineering. Acta Biomater. 2013;9:7308–19.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Chen L, Hu J, Ran J, Shen X, Tong H. Preparation and evaluation of collagen-silk fibroin/hydroxyapatite nanocomposites for bone tissue engineering. Int J Biol Macromol. 2014;65:1–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhao C, Tan A, Pastorin G, Ho HK. Nanomaterial scaffolds for stem cell proliferation and differentiation in tissue engineering. Biotechnol Adv. 2013;31:654–68.PubMedCrossRefGoogle Scholar
  16. 16.
    Tägil M, Johnsson R. Incomplete incorporation of morselized and impacted autologous bone graft: a histological study in 4 intracorporally grafted lumbar fractures. Acta Orthop. 1999;70:555–8.CrossRefGoogle Scholar
  17. 17.
    Rodrigues AI, Gomes ME, Leonor IB, Reis RL. Bioactive starch-based scaffolds and human adipose stem cells are a good combination for bone tissue engineering. Acta Biomater. 2012;8:3765–76.PubMedCrossRefGoogle Scholar
  18. 18.
    De Gorter DJJ, Van Dinther M, Korchynskyi O, Ten Dijke P. Biphasic effects of transforming growth factor? On bone morphogenetic protein-induced osteoblast differentiation. J Bone Miner Res. 2011;26:1178–87.PubMedCrossRefGoogle Scholar
  19. 19.
    Buckwalter JA, Glimcher MJ, Becker RR. Bone biology. J Bone Joint Surg Instr Course Lect. 1995;77:1256–75.CrossRefGoogle Scholar
  20. 20.
    Sottile V, Thomson A, McWhir J. In vitro osteogenic differentiation of human ES cells. Cloning Stem Cells. 2003;5:149–55.PubMedCrossRefGoogle Scholar
  21. 21.
    Levi B, Hyun JS, Montoro DT, Lo DD, Chan CKF, Hu S, et al. In vivo directed differentiation of pluripotent stem cells for skeletal regeneration. Proc Natl Acad Sci USA. 2012;109:20379–84.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Krishnamurithy G, Murali MR, Hamdi M, Abbas AA, Raghavendran HB, Kamarul T. Characterization of bovine-derived porous hydroxyapatite scaffold and its potential to support osteogenic differentiation of human bone marrow derived mesenchymal stem cells. Ceram Int. 2014;40:771–7.CrossRefGoogle Scholar
  23. 23.
    Bielby RC, Boccaccini AR, Polak JM, Buttery LDK. In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng. 2004;10:1518–25.PubMedCrossRefGoogle Scholar
  24. 24.
    Buttery LD, Bourne S, Xynos JD, Wood H, Hughes FJ, Hughes SP, et al. Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng. 2001;7:89–99.PubMedCrossRefGoogle Scholar
  25. 25.
    Lees JG, Lim SA, Croll T, Williams G, Lui S, Cooper-White J, et al. Transplantation of 3D scaffolds seeded with human embryonic stem cells: biological features of surrogate tissue and teratoma-forming potential. Regen Med. 2007;2:289–300.PubMedCrossRefGoogle Scholar
  26. 26.
    Shin M, Yoshimoto H, Vacanti JP. In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold. Tissue Eng. 2004;10:33–41.PubMedCrossRefGoogle Scholar
  27. 27.
    Wan C, He Q, Li G. Allogenic peripheral blood derived mesenchymal stem cells (MSCs) enhance bone regeneration in rabbit ulna critical-sized bone defect model. J Orthop Res. 2006;24:610–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Lu W, Ji K, Kirkham J, Yan Y, Boccaccini AR, Kellett M, et al. Bone tissue engineering by using a combination of polymer/bioglass composites with human adipose-derived stem cells. Cell Tissue Res. 2014;356:97–107.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang Z-Y, Teoh S-H, Chong MSK, Schantz JT, Fisk NM, Choolani MA, et al. Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells. 2009;27:126–37.PubMedCrossRefGoogle Scholar
  30. 30.
    Ardeshirylajimi A, Hosseinkhani S, Parivar K, Yaghmaie P, Soleimani M. Nanofiber-based polyethersulfone scaffold and efficient differentiation of human induced pluripotent stem cells into osteoblastic lineage. Mol Biol Rep. 2013;40:4287–94.PubMedCrossRefGoogle Scholar
  31. 31.
    Li F, Niyibizi C. Cells derived from murine induced pluripotent stem cells (iPSC) by treatment with members of TGF-beta family give rise to osteoblasts differentiation and form bone in vivo. BMC Cell Biol. 2012;13:35.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Ye J-H, Xu Y-J, Gao J, Yan S-G, Zhao J, Tu Q, et al. Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs. Biomaterials. 2011;32:5065–76.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Jin G-Z, Kim T-H, Kim J-H, Won J-E, Yoo S-Y, Choi S-J, et al. Bone tissue engineering of induced pluripotent stem cells cultured with macrochanneled polymer scaffold. J Biomed Mater Res A. 2013;101:1283–91.PubMedCrossRefGoogle Scholar
  34. 34.
    Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z, et al. Umbilical cord Wharton’s Jelly: a new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Eng Part A. 2009;15:2325–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Stanko P, Kaiserova K, Altanerova V, Altaner C. Comparison of human mesenchymal stem cells derived from dental pulp, bone marrow, adipose tissue, and umbilical cord tissue by gene expression. Biomed Pap Med Fac Univ Palacký Olomouc Czechoslov. 2014;158:373–7.CrossRefGoogle Scholar
  36. 36.
    TheinHan W, Weir MD, Simon CG, Xu HHK. Non-rigid calcium phosphate cement containing hydrogel microbeads and absorbable fibres seeded with umbilical cord stem cells for bone engineering. J Tissue Eng Regen Med. 2013;7:777–87.PubMedGoogle Scholar
  37. 37.
    Rodrigues MT, Lee SJ, Gomes ME, Reis RL, Atala A, Yoo JJ. Amniotic fluid-derived stem cells as a cell source for bone tissue engineering. Tissue Eng Part A. 2012;18:2518–27.PubMedCrossRefGoogle Scholar
  38. 38.
    Diao Y, Ma Q, Cui F, Zhong Y. Human umbilical cord mesenchymal stem cells: osteogenesis in vivo as seed cells for bone tissue engineering. J Biomed Mater Res A. 2009;91:123–31.PubMedCrossRefGoogle Scholar
  39. 39.
    Kim J, Jeong SY, Ju YM, Yoo JJ, Smith TL, Khang G, et al. In vitro osteogenic differentiation of human amniotic fluid-derived stem cells on a poly(lactide-co-glycolide) (PLGA)-bladder submucosa matrix (BSM) composite scaffold for bone tissue engineering. Biomed Mater. 2013;8:014107.PubMedCrossRefGoogle Scholar
  40. 40.
    Riccio M, Maraldi T, Pisciotta A, La Sala GB, Ferrari A, Bruzzesi G, et al. Fibroin scaffold repairs critical-size bone defects in vivo supported by human amniotic fluid and dental pulp stem cells. Tissue Eng Part A. 2012;18:1006–13.PubMedCrossRefGoogle Scholar
  41. 41.
    Maraldi T, Riccio M, Pisciotta A, Zavatti M, Carnevale G, Beretti F, et al. Human amniotic fluid-derived and dental pulp-derived stem cells seeded into collagen scaffold repair critical-size bone defects promoting vascularization. Stem Cell Res Ther. 2013;4:53.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Akkouch A, Zhang Z, Rouabhia M. Engineering bone tissue using human dental pulp stem cells and an osteogenic collagen-hydroxyapatite-poly (l-lactide-co-ε-caprolactone) scaffold. J Biomater Appl. 2014;28:922–36.PubMedCrossRefGoogle Scholar
  43. 43.
    Asutay F, Polat S, Gül M, Subaşı C, Kahraman SA, Karaöz E. The effects of dental pulp stem cells on bone regeneration in rat calvarial defect model: Micro-computed tomography and histomorphometric analysis. Arch Oral Biol. 2015;60:1729–35.PubMedCrossRefGoogle Scholar
  44. 44.
    Song K, Rao N-J, Chen M-L, Huang Z-J, Cao Y-G. Enhanced bone regeneration with sequential delivery of basic fibroblast growth factor and sonic hedgehog. Injury. 2011;42:796–802.PubMedCrossRefGoogle Scholar
  45. 45.
    Caplan AI, Correa D. PDGF in bone formation and regeneration: new insights into a novel mechanism involving MSCs. J Orthop Res. 2011;29:1795–803.PubMedCrossRefGoogle Scholar
  46. 46.
    Ochiai H, Okada S, Saito A, Hoshi K, Yamashita H, Takato T, et al. Inhibition of insulin-like growth factor-1 (IGF-1) expression by prolonged transforming growth factor-β1 (TGF-β1) administration suppresses osteoblast differentiation. J Biol Chem. 2012;287:22654–61.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Peng H, Wright V, Usas A, Gearhart B, Shen HC, Cummins J, et al. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest. 2002;110:751–9.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Luu HH, Song W-X, Luo X, Manning D, Luo J, Deng Z-L, et al. Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells. J Orthop Res. 2007;25:665–77.PubMedCrossRefGoogle Scholar
  49. 49.
    Cooper GM, Miller ED, Decesare GE, Usas A, Lensie EL, Bykowski MR, et al. Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation. Tissue Eng Part A. 2010;16:1749–59.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Yang S, Wei D, Wang D, Phimphilai M, Krebsbach PH, Franceschi RT. In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. J Bone Miner Res. 2003;18:705–15.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Park K-H, Kim H, Moon S, Na K. Bone morphogenic protein-2 (BMP-2) loaded nanoparticles mixed with human mesenchymal stem cell in fibrin hydrogel for bone tissue engineering. J Biosci Bioeng. 2009;108:530–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Jun S-H, Lee E-J, Jang T-S, Kim H-E, Jang J-H, Koh Y-H. Bone morphogenic protein-2 (BMP-2) loaded hybrid coating on porous hydroxyapatite scaffolds for bone tissue engineering. J Mater Sci Mater Med. 2013;24:773–82.PubMedCrossRefGoogle Scholar
  53. 53.
    Florczyk SJ, Leung M, Jana S, Li Z, Bhattarai N, Huang JI, et al. Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor. J Biomed Mater Res A. 2012;100:3408–15.PubMedCrossRefGoogle Scholar
  54. 54.
    Shah NJ, Hyder MN, Quadir MA, Dorval Courchesne N-M, Seeherman HJ, Nevins M, et al. Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction. Proc Natl Acad Sci USA. 2014;111:12847–52.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Tabata Y, Yamada K, Miyamoto S, Nagata I, Kikuchi H, Aoyama I, et al. Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels. Biomaterials. 1998;19:807–15.PubMedCrossRefGoogle Scholar
  56. 56.
    Tabata Y, Yamada K, Hong L, Miyamoto S, Hashimoto N, Ikada Y. Skull bone regeneration in primates in response to basic fibroblast growth factor. J Neurosurg. 1999;91:851–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Kang MS, Kim J-H, Singh RK, Jang J-H, Kim H-W. Therapeutic-designed electrospun bone scaffolds: mesoporous bioactive nanocarriers in hollow fiber composites to sequentially deliver dual growth factors. Acta Biomater. 2015;16:103–16.PubMedCrossRefGoogle Scholar
  58. 58.
    Lee YM, Park YJ, Lee SJ, Ku Y, Han SB, Klokkevold PR, et al. The bone regenerative effect of platelet-derived growth factor-BB delivered with a chitosan/tricalcium phosphate sponge carrier. J Periodontol. 2000;71:418–24.PubMedCrossRefGoogle Scholar
  59. 59.
    Lynch SE, Williams RC, Poison AM, Howell TH, Reddy MS, Zappa UE, et al. A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration. J Clin Periodontol. 1989;16:545–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Thoma DS, Jung RE, Hänseler P, Hämmerle CHF, Cochran DL, Weber FE. Impact of recombinant platelet-derived growth factor BB on bone regeneration: a study in rabbits. Int J Periodontics Restor Dent. 2012;32:195–202.Google Scholar
  61. 61.
    Behnia H, Khojasteh A, Soleimani M, Tehranchi A, Atashi A. Repair of alveolar cleft defect with mesenchymal stem cells and platelet derived growth factors: a preliminary report. J Craniomaxillofac Surg. 2012;40:2–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Nevins M, Kao RT, McGuire MK, McClain PK, Hinrichs JE, McAllister BS, et al. Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. J Periodontol. 2013;84:456–64.PubMedCrossRefGoogle Scholar
  63. 63.
    Tong S, Xue L, Xu D, Liu Z, Wang X. In vitro culture of BMSCs on VEGF-SF-CS three-dimensional scaffolds for bone tissue engineering. J Hard Tissue Biol. 2015;24:123–33.CrossRefGoogle Scholar
  64. 64.
    Jabbarzadeh E, Deng M, Lv Q, Jiang T, Khan YM, Nair LS, et al. VEGF-incorporated biomimetic poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering. J Biomed Mater Res B Appl Biomater. 2012;100:2187–96.PubMedCrossRefGoogle Scholar
  65. 65.
    Koç A, Finkenzeller G, Elçin AE, Stark GB, Elçin YM. Evaluation of adenoviral vascular endothelial growth factor-activated chitosan/hydroxyapatite scaffold for engineering vascularized bone tissue using human osteoblasts: in vitro and in vivo studies. J Biomater Appl. 2014;29:748–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Samee M, Kasugai S, Kondo H, Ohya K, Shimokawa H, Kuroda S. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentiation and bone formation. J Pharmacol Sci. 2008;108:18–31.PubMedCrossRefGoogle Scholar
  67. 67.
    Yu Y, Mu J, Fan Z, Lei G, Yan M, Wang S, et al. Insulin-like growth factor 1 enhances the proliferation and osteogenic differentiation of human periodontal ligament stem cells via ERK and JNK MAPK pathways. Histochem Cell Biol. 2012;137:513–25.PubMedCrossRefGoogle Scholar
  68. 68.
    Granero-Moltó F, Myers TJ, Weis JA, Longobardi L, Li T, Yan Y, et al. Mesenchymal stem cells expressing insulin-like growth factor-I (MSCIGF) promote fracture healing and restore new bone formation in Irs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects. Stem Cells. 2011;29:1537–48.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Barhanpurkar AP, Gupta N, Srivastava RK, Tomar GB, Naik SP, Joshi SR, et al. IL-3 promotes osteoblast differentiation and bone formation in human mesenchymal stem cells. Biochem Biophys Res Commun. 2012;418:669–75.PubMedCrossRefGoogle Scholar
  70. 70.
    Li W, Nooeaid P, Roether JA, Schubert DW, Boccaccini AR. Preparation and characterization of vancomycin releasing PHBV coated 45S5 Bioglass?-based glass-ceramic scaffolds for bone tissue engineering. J Eur Ceram Soc. 2014;34:505–14.CrossRefGoogle Scholar
  71. 71.
    Torres L, Gaspar VM, Serra IR, Diogo GS, Fradique R, Silva AP, et al. Bioactive polymeric-ceramic hybrid 3D scaffold for application in bone tissue regeneration. Mater Sci Eng C Mater Biol Appl. 2013;33:4460–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Okazaki Y, Gotoh E. Metal release from stainless steel, Co–Cr–Mo–Ni–Fe and Ni–Ti alloys in vascular implants. Corros Sci. 2008;50:3429–38.CrossRefGoogle Scholar
  73. 73.
    Lobo SE, Arinzeh TL. Biphasic calcium phosphate ceramics for bone regeneration and tissue engineering applications. Materials (Basel). 2010;3:815–26.CrossRefGoogle Scholar
  74. 74.
    Sanosh KP, Gervaso F, Sannino A, Licciulli A. Preparation and characterization of Collagen/hydroxyapatite microsphere composite scaffold for bone regeneration. Key Eng Mater. 2013;587:239–44.CrossRefGoogle Scholar
  75. 75.
    Vagaska B, Bacakova L, Filová E, Balik K. Osteogenic cells on bio-inspired materials for bone tissue engineering. Physiol Res. 2010;59:309–22.PubMedGoogle Scholar
  76. 76.
    Liao CZ, Li K, Wong HM, Tong WY, Yeung KWK, Tjong SC. Novel polypropylene biocomposites reinforced with carbon nanotubes and hydroxyapatite nanorods for bone replacements. Mater Sci Eng C. 2013;33:1380–8.CrossRefGoogle Scholar
  77. 77.
    Alvarez K, Hyun S, Nakano T. In vivo osteocompatibility of lotus-type porous nickel-free stainless steel in rats. Mater Sci Eng C. 2009;29:1182–90.CrossRefGoogle Scholar
  78. 78.
    Matsuno H. Biocompatibility and osteogenesis of refractory metal implants, titanium, hafnium, niobium, tantalum and rhenium. Biomaterials. 2001;22:1253–62.PubMedCrossRefGoogle Scholar
  79. 79.
    Michel R, Nolte M, Reich M, Löer F. Systemic effects of implanted prostheses made of cobalt-chromium alloys. Arch Orthop Trauma Surg. 1991;110:61–74.PubMedCrossRefGoogle Scholar
  80. 80.
    Goodman S, Fornasier V. The effects of bulk versus particulate titanium and cobalt chrome alloy implanted into the rabbit tibia. J Biomed Mater Res A. 1990;24:1539–49.CrossRefGoogle Scholar
  81. 81.
    Kapanen A, Ryhänen J, Danilov A, Tuukkanen J. Effect of nickel–titanium shape memory metal alloy on bone formation. Biomaterials. 2001;22:2475–80.PubMedCrossRefGoogle Scholar
  82. 82.
    Long M, Rack H. Titanium alloys in total joint replacement—a materials science perspective. Biomaterials. 1998;19:1621–39.PubMedCrossRefGoogle Scholar
  83. 83.
    Alvarez K, Nakajima H. Metallic scaffolds for bone regeneration. Materials (Basel). 2009;2:790–832.PubMedCentralCrossRefGoogle Scholar
  84. 84.
    Fan JP, Kalia P, Di Silvio L, Huang J. In vitro response of human osteoblasts to multi-step sol–gel derived bioactive glass nanoparticles for bone tissue engineering. Mater Sci Eng C. 2014;36:206–14.CrossRefGoogle Scholar
  85. 85.
    Paşcu EI, Stokes J, McGuinness GB. Electrospun composites of PHBV, silk fibroin and nano-hydroxyapatite for bone tissue engineering. Mater Sci Eng C. 2013;33:4905–16.CrossRefGoogle Scholar
  86. 86.
    Wu C, Fan W, Zhou Y, Luo Y, Gelinsky M, Chang J, et al. 3D-printing of highly uniform CaSiO3 ceramic scaffolds: preparation, characterization and in vivo osteogenesis. J Mater Chem. 2012;22:12288.CrossRefGoogle Scholar
  87. 87.
    Ivan FD, Marian A, Tanase CE, Butnaru M, Vereştiuc L. Biomimetic composites based on calcium phosphates and chitosan-hyaluronic acid with potential application in bone tissue engineering. Key Eng Mater. 2013;587:191–6.CrossRefGoogle Scholar
  88. 88.
    Zhang J, Zhao S, Zhu Y, Huang Y, Zhu M, Tao C, et al. Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration. Acta Biomater. 2014;10:2269–81.PubMedCrossRefGoogle Scholar
  89. 89.
    Xynos ID, Hukkanen MVJ, Batten JJ, Buttery LD, Hench LL, Polak JM. Bioglass ®45S5 stimulates osteoblast turnover and enhances bone formation in vitro: Implications and applications for bone tissue engineering. Calcif Tissue Int. 2000;67:321–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Izadi S, Hesaraki S, Hafezi-Ardakani M. Evaluation nanostructure properties of bioactive glass scaffolds for bone tissue engineering. Adv Mater Res. 2013;829:289–93.CrossRefGoogle Scholar
  91. 91.
    Ravichandran R, Sundaramurthi D, Gandhi S, Sethuraman S, Krishnan UM. Bioinspired hybrid mesoporous silica-gelatin sandwich construct for bone tissue engineering. Microporous Mesoporous Mater. 2014;187:53–62.CrossRefGoogle Scholar
  92. 92.
    Le Nihouannen D, Duval L, Lecomte A. Interactions of total bone marrow cells with increasing quantities of macroporous calcium phosphate ceramic granules. J Mater Sci Mater Med. 2007;18:1983–90.CrossRefGoogle Scholar
  93. 93.
    Schwartz C, Liss P, Jacquemaire B. Biphasic synthetic bone substitute use in orthopaedic and trauma surgery: clinical, radiological and histological results. J Mater Sci Mater Med. 1999;10:821–5.PubMedCrossRefGoogle Scholar
  94. 94.
    Rath SN, Strobel LA, Arkudas A, Beier JP, Maier A-K, Greil P, et al. Osteoinduction and survival of osteoblasts and bone-marrow stromal cells in 3D biphasic calcium phosphate scaffolds under static and dynamic culture conditions. J Cell Mol Med. 2012;16:2350–61.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Scalera F, Gervaso F, Sanosh KP, Palamà IE, Dimida S, Sannino A. Development of a novel hybrid porous scaffold for bone tissue engineering: forsterite nanopowder reinforced chitosan. Key Eng Mater. 2014;587:249–54.CrossRefGoogle Scholar
  96. 96.
    Maquet V, Jerome R. Design of macroporous biodegradable polymer scaffolds for cell transplantation. Mater Sci Forum. 1997;250:15–42.CrossRefGoogle Scholar
  97. 97.
    Tsai K, Kao S, Wang C. Type I collagen promotes proliferation and osteogenesis of human mesenchymal stem cells via activation of ERK and Akt pathways. … Res Part A. 2010;94:673–82.Google Scholar
  98. 98.
    Kruger TE, Miller AH, Wang J. Collagen scaffolds in bone sialoprotein-mediated bone regeneration. Sci World J. 2013;2013:812718.CrossRefGoogle Scholar
  99. 99.
    Wang J, Yu X. Preparation, characterization and in vitro analysis of novel structured nanofibrous scaffolds for bone tissue engineering. Acta Biomater. 2010;6:3004–12.PubMedCrossRefGoogle Scholar
  100. 100.
    Duarte A, Mano J, Reis R. Novel 3D scaffolds of chitosan–PLLA blends for tissue engineering applications: preparation and characterization. J Supercrit Fluids. 2010;54:282–9.CrossRefGoogle Scholar
  101. 101.
    Muzzarelli R, Zucchini C, Ilari P. Osteoconductive properties of methylpyrrolidinone chitosan in an animal model. Biomaterials. 1993;14:925–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Kavya KC, Jayakumar R, Nair S, Chennazhi KP. Fabrication and characterization of chitosan/gelatin/nSiO2 composite scaffold for bone tissue engineering. Int J Biol Macromol. 2013;59:255–63.PubMedCrossRefGoogle Scholar
  103. 103.
    Correia SI, Pereira H, Silva-Correia J, Van Dijk CN, Espregueira-Mendes J, Oliveira JM, et al. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint. J R Soc Interface. 2014;11:20130784.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Zang S, Zhuo Q, Chang X, Qiu G, Wu Z, Yang G. Study of osteogenic differentiation of human adipose-derived stem cells (HASCs) on bacterial cellulose. Carbohydr Polym. 2014;104:158–65.PubMedCrossRefGoogle Scholar
  105. 105.
    Liuyun J, Yubao L, Chengdong X. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering. J Biomed Sci. 2009;16:65.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Sun H, Zhu F, Hu Q, Krebsbach PH. Controlling stem cell-mediated bone regeneration through tailored mechanical properties of collagen scaffolds. Biomaterials. 2014;35:1176–84.PubMedCrossRefGoogle Scholar
  107. 107.
    Chahala S, Hussain FSJ, Yusoff MM. Characterization of modified cellulose (MC)/poly (vinyl alcohol) electrospun nanofibers for bone tissue engineering. Procedia Eng. 2013;53:683–8.CrossRefGoogle Scholar
  108. 108.
    Boccaccini AR, Notingher I, Maquet V, Jerome R. Bioresorbable and bioactive composite materials based on polylactide foams filled with and coated by Bioglass® particles for tissue engineering applications. J mater sci. Mater med. 2003;14:443–50.Google Scholar
  109. 109.
    Xu H, Han D, Dong J-S, Shen G-X, Chai G, Yu Z-Y, et al. Rapid prototyped PGA/PLA scaffolds in the reconstruction of mandibular condyle bone defects. Int J Med Robot. 2010;6:66–72.PubMedCrossRefGoogle Scholar
  110. 110.
    Fujihara K, Kotaki M, Ramakrishna S. Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers. Biomaterials. 2005;26:4139–47.PubMedCrossRefGoogle Scholar
  111. 111.
    Kim H, Song J, Kim H. Nanofiber generation of gelatin–hydroxyapatite biomimetics for guided tissue regeneration. Adv Funct Mater. 2005;15:1988–94.CrossRefGoogle Scholar
  112. 112.
    Li C, Vepari C, Jin H, Kim H, Kaplan D. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials. 2006;27:3115–24.PubMedCrossRefGoogle Scholar
  113. 113.
    Sui G, Yang X, Mei F, Hu X. Poly-L-lactic acid/hydroxyapatite hybrid membrane for bone tissue regeneration. J Biomed Mater Res A. 2007;82:445–54.PubMedCrossRefGoogle Scholar
  114. 114.
    Catledge S, Clem W. An electrospun triphasic nanofibrous scaffold for bone tissue engineering. Biomed Mater. 2007;2:142.PubMedCrossRefGoogle Scholar
  115. 115.
    Rainer A, Spadaccio C, Sedati P, De Marco F, Carotti S, Lusini M, et al. Electrospun hydroxyapatite-functionalized PLLA scaffold: potential applications in sternal bone healing. Ann Biomed Eng. 2011;39:1882–90.PubMedCrossRefGoogle Scholar
  116. 116.
    Jaiswal AK, Kadam SS, Soni VP, Bellare JR. Improved functionalization of electrospun PLLA/gelatin scaffold by alternate soaking method for bone tissue engineering. Appl Surf Sci. 2013;268:477–88.CrossRefGoogle Scholar
  117. 117.
    Alves A, Duarte ARC, Mano JF, Sousa RA, Reis RL. PDLLA enriched with ulvan particles as a novel 3D porous scaffold targeted for bone engineering. J Supercrit Fluids. 2012;65:32–8.CrossRefGoogle Scholar
  118. 118.
    Sajesh KM, Jayakumar R, Nair SV, Chennazhi KP. Biocompatible conducting chitosan/polypyrrole-alginate composite scaffold for bone tissue engineering. Int J Biol Macromol. 2013;62:465–71.PubMedCrossRefGoogle Scholar
  119. 119.
    Zhang RY, Ma PX. Poly(alpha-hydroxyl acids) hydroxyapatite porous composites for bone-tissue engineering. I. Preparation and morphology. J Biomed Mater Res. 1999;44:446–55.PubMedCrossRefGoogle Scholar
  120. 120.
    Polini A, Pisignano D, Parodi M, Quarto R, Scaglione S. Osteoinduction of human mesenchymal stem cells by bioactive composite scaffolds without supplemental osteogenic growth factors. PLoS One. 2011;6:1–8.CrossRefGoogle Scholar
  121. 121.
    Marra KG, Szem JW, Kumta PN, DiMilla PA, Weiss LE. In vitro analysis of biodegradable polymer blend/hydroxyapatite composites for bone tissue engineering. J Biomed Mater Res. 1999;47:324–35.PubMedCrossRefGoogle Scholar
  122. 122.
    Gonçalves EM, Oliveira FJ, Silva RF, Neto MA, Fernandes MH, Amaral M, et al. Three-dimensional printed PCL-hydroxyapatite scaffolds filled with CNTs for bone cell growth stimulation. J Biomed Mater Res B Appl Biomater. 2015. doi: 10.1002/jbm.b.33432.PubMedCrossRefGoogle Scholar
  123. 123.
    Singh RK, Patel KD, Lee JH, Lee E-J, Kim J-H, Kim T-H, et al. Potential of magnetic nanofiber scaffolds with mechanical and biological properties applicable for bone regeneration. PLoS One. 2014;9:e91584.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Ma H, Su W, Tai Z, Sun D, Yan X, Liu B, et al. Preparation and cytocompatibility of polylactic acid/hydroxyapatite/graphene oxide nanocomposite fibrous membrane. Chin Sci Bull. 2012;57:3051–8.CrossRefGoogle Scholar
  125. 125.
    Qian J, Xu W, Yong X, Jin X, Zhang W. Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering. Mater Sci Eng C Mater Biol Appl. 2014;36:95–101.PubMedCrossRefGoogle Scholar
  126. 126.
    Cheng CW, Solorio LD, Alsberg E. Decellularized tissue and cell-derived extracellular matrices as scaffolds for orthopaedic tissue engineering. Biotechnol Adv. 2014;32:462–84.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Liu Y, Dang Z, Wang Y, Huang J, Li H. Hydroxyapatite/graphene-nanosheet composite coatings deposited by vacuum cold spraying for biomedical applications: inherited nanostructures and enhanced properties. Carbon N Y. 2014;67:250–9.CrossRefGoogle Scholar
  128. 128.
    Wang X, Li Y. Biomimetic modification of porous TiNbZr alloy scaffold for bone tissue engineering. Tissue Eng Part A. 2009;16:309–16.CrossRefGoogle Scholar
  129. 129.
    Chowdhury S, Lalwani G, Zhang K. Cell specific cytotoxicity and uptake of graphene nanoribbons. Biomaterials. 2013;34:283–93.CrossRefGoogle Scholar
  130. 130.
    Agarwal S, Zhou X, Ye F, He Q, Chen GCK, Soo J, et al. Interfacing live cells with nanocarbon substrates. Langmuir. 2010;26:2244–7.PubMedCrossRefGoogle Scholar
  131. 131.
    Wermelin K, Suska F, Tengvall P, Thomsen P, Aspenberg P. Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats. Bone. 2008;42:365–71.PubMedCrossRefGoogle Scholar
  132. 132.
    Hunt JA, Callaghan JT, Sutcliffe CJ, Morgan RH, Halford B, Black RA. The design and production of Co-Cr alloy implants with controlled surface topography by CAD-CAM method and their effects on osseointegration. Biomaterials. 2005;26:5890–7.PubMedCrossRefGoogle Scholar
  133. 133.
    Wu C, Han P, Liu X, Xu M, Tian T, Chang J, et al. Mussel-inspired bioceramics with self-assembled Ca-P/polydopamine composite nanolayer: preparation, formation mechanism, improved cellular bioactivity and osteogenic differentiation of bone marrow stromal cells. Acta Biomater. 2014;10:428–38.PubMedCrossRefGoogle Scholar
  134. 134.
    Feng P, Wei P, Shuai C, Peng S. Characterization of mechanical and biological properties of 3-D scaffolds reinforced with zinc oxide for bone tissue engineering. PLoS One. 2014;9:e87755.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Salgado AJ, Figueiredo JE, Coutinho OP, Reis RL. Biological response to pre-mineralized starch based scaffolds for bone tissue engineering. J Mater Sci Mater Med. 2005;16:267–75.PubMedCrossRefGoogle Scholar
  136. 136.
    Roether JA, Gough JE, Boccaccini AR, Hench LL, Maquet V, Jérôme R. Novel bioresorbable and bioactive composites based on bioactive glass and polylactide foams for bone tissue engineering. J Mater Sci Mater Med. 2002;13:1207–14.PubMedCrossRefGoogle Scholar
  137. 137.
    Kao C-T, Lin C-C, Chen Y-W, Yeh C-H, Fang H-Y, Shie M-Y. Poly(dopamine) coating of 3D printed poly(lactic acid) scaffolds for bone tissue engineering. Mater Sci Eng C. 2015;56:165–73.CrossRefGoogle Scholar
  138. 138.
    Togami W, Sei A, Okada T, Taniwaki T, Fujimoto T, Nakamura T et al. Effects of water-holding capability of the PVF sponge on the adhesion and differentiation of rat bone marrow stem cell culture. J Biomed Mater Res A. 2013;102(1):1–33. Google Scholar
  139. 139.
    Oliveira AL, Costa SA, Sousa RA, Reis RL. Nucleation and growth of biomimetic apatite layers on 3D plotted biodegradable polymeric scaffolds: effect of static and dynamic coating conditions. Acta Biomater. 2009;5:1626–38.PubMedCrossRefGoogle Scholar
  140. 140.
    Pittenger MF. Multilineage potential of adult human mesenchymal stem cells. Science (80). 1999;284:143–47.Google Scholar
  141. 141.
    Janssen FW, Oorschot A Van, Oostra J, Bruijn JD De. Flow perfusion improves seeding of tissue engineering scaffolds with different architectures. Ann biomed eng. 2007;35:429–442.Google Scholar
  142. 142.
    Mygind T, Stiehler M, Baatrup A, Li H, Zou X, Flyvbjerg A, et al. Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. Biomaterials. 2007;28:1036–47.PubMedCrossRefGoogle Scholar
  143. 143.
    Janssen FW, van Dijkhuizen-Radersma R, Van Oorschot A, Oostra J, De Bruijn JD. CAVB. Human tissue-engineered bone produced in clinically relevant amounts using a semi-automated perfusion bioreactor system: a preliminary study. J Tissue Eng Regen Med. 2010;4:12–24.PubMedCrossRefGoogle Scholar
  144. 144.
    Grayson WL, Marolt D, Bhumiratana S, Fröhlich M, Guo XE, Vunjak-Novakovic G. Optimizing the medium perfusion rate in bone tissue engineering bioreactors. Biotechnol Bioeng. 2011;108:1159–70.PubMedCrossRefGoogle Scholar
  145. 145.
    Liu Y, Teoh SH, Chong MS, Yeow CH, Kamm RD, Choolani MCJ. Contrasting effects of vasculogenic induction upon biaxial bioreactor stimulation of mesenchymal stem cells and endothelial progenitor cells cocultures in 3D scaffolds under in vitro and in vivo paradigms for vascularized bone tissue engineering. Tissue Eng Part A. 2013;7:893–904.CrossRefGoogle Scholar
  146. 146.
    Yeatts AB, Fisher JP. Bone tissue engineering bioreactors: dynamic culture and the influence of shear stress. Bone. 2011;48:171–81.PubMedCrossRefGoogle Scholar
  147. 147.
    Meinel L, Karageorgiou V, Fajardo R, Snyder B, Shinde-Patil V, Zichner L, et al. Bone tissue engineering using human mesenchymal stem cells: effects of scaffold material and medium flow. Ann Biomed Eng. 2004;32:112–22.PubMedCrossRefGoogle Scholar
  148. 148.
    Janssen FW, Oostra J, Oorschot A Van, Blitterswijk CA Van. A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. 2006; 27:315–23.Google Scholar
  149. 149.
    Yeatts AB, Both SK, Yang W, Alghamdi HS, Yang F. et al. In vivo bone regeneration using tubular perfusion system bioreactor cultured nanofibrous scaffolds. Tissue Eng Part A 2013. (Accessed 15 Dec 2015).
  150. 150.
    Thibault RA, Mikos AG, Kasper FK. Protein and mineral composition of osteogenic extracellular matrix constructs generated with a flow perfusion bioreactor. Biomacromolecules. 2011;12:4204–12.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Kleinhans C, Mohan RR, Vacun G, Schwarz T, Haller B, Sun Y, et al. A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects. Biotechnol J. 2015. doi: 10.1002/biot.201400813.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Lambrechts T, Papantoniou I, Viazzi S, Bovy T, Schrooten J, Luyten FP, et al. Evaluation of a monitored multiplate bioreactor for large-scale expansion of human periosteum derived stem cells for bone tissue engineering applications. Biochem Eng J. 2015. doi: 10.1016/j.bej.2015.07.015.CrossRefGoogle Scholar
  153. 153.
    Li M, Tilles AW, Milwid JM, Hammad M, Lee J, Yarmush ML, et al. Phenotypic and functional characterization of human bone marrow stromal cells in hollow-fibre bioreactors. J Tissue Eng Regen Med. 2012;6:369–77.PubMedCrossRefGoogle Scholar
  154. 154.
    VanGordon SB, Voronov RS, Blue TB, Shambaugh RL, Papavassiliou DV, Sikavitsas VI. Effects of scaffold architecture on preosteoblastic cultures under continuous fluid shear. Ind Eng Chem Res. 2011;50:620–9.CrossRefGoogle Scholar
  155. 155.
    Urist M. Bone formation by autoinduction. Science (80). 1965; 150:893–899.Google Scholar
  156. 156.
    Report #A322, “U.S. Markets for Orthopedic Biomaterials for Viscosupplementation and Cartilage, Ligament, and Tendon Repair and Regeneration. 2015. (Accessed 21 Nov 2015).

Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Shivaji Kashte
    • 1
    • 3
  • Amit Kumar Jaiswal
    • 2
  • Sachin Kadam
    • 3
  1. 1.Department of Biosciences and TechnologyDefence Institute of Advanced TechnologyGirinagar, PuneIndia
  2. 2.Center for Biomaterials, Cellular and Molecular TheranosticsVIT UniversityVelloreIndia
  3. 3.Center for Interdisciplinary ResearchD. Y. Patil UniversityKolhapurIndia

Personalised recommendations