Advertisement

International Orthopaedics

, Volume 38, Issue 9, pp 1877–1884 | Cite as

Nanobiotechnology and bone regeneration: a mini-review

  • Nadomir Gusić
  • Alan IvkovićEmail author
  • John VaFaye
  • Andreja Vukasović
  • Jana Ivković
  • Damir Hudetz
  • Saša Janković
Review Article

Abstract

The purpose of this paper is to review current developments in bone tissue engineering, with special focus on the promising role of nanobiotechnology. This unique fusion between nanotechnology and biotechnology offers unprecedented possibilities in studying and modulating biological processes on a molecular and atomic scale. First we discuss the multiscale hierarchical structure of bone and its implication on the design of new scaffolds and delivery systems. Then we briefly present different types of nanostructured scaffolds, and finally we conclude with nanoparticle delivery systems and their potential use in promoting bone regeneration. This review is not meant to be exhaustive and comprehensive, but aims to highlight concepts and key advances in the field of nanobiotechnology and bone regeneration.

Keywords

Bone Nanotechnology Scaffold Drug delivery Cell seeding 

Notes

Acknowledgments

This project has received funding from the European Union’s Seventh Programme for research, technological development and demonstration under grant agreement No.278807.

References

  1. 1.
    Giannoudis PV, Dinopoulus H, Tsiridis E (2005) Bone substitutes: an update. Injury 36:S20–S27PubMedCrossRefGoogle Scholar
  2. 2.
    Wheeler DL, Enneking WF (2005) Allograft bone decreases in strength in vivo over time. Clin Orthop Relat Res 435:36–42PubMedCrossRefGoogle Scholar
  3. 3.
    Yang Y (2009) Skeletal morphogenesis during embryonic development. Crit Rev Eukaryot Gene Expr 19(3):197–218PubMedCrossRefGoogle Scholar
  4. 4.
    Ivkovic A, Marijanovic I, Hudetz D, Porter RM, Pecina M, Evans CH (2011) Regenerative medicine and tissue engineering in orthopaedic surgery. Front Biosci (Elite Ed) 3:923–944Google Scholar
  5. 5.
    Hernigou P, Pariat J, Queinnec S, Homma Y, Lachaniette CH, Chevallier N et al (2014) Supercharging irradiated allografts with mesenchymal stem cells improves acetabular bone grafting in revision arthroplasty. Int OrthopGoogle Scholar
  6. 6.
    Wang X, Wang Y, Gou W, Lu Q, Peng J, Lu S (2013) Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. Int Orthop 37(12):2491–2498PubMedCrossRefGoogle Scholar
  7. 7.
    Vukicevic S, Oppermann H, Verbanac D, Jankolija M, Popek I, Curak J et al (2014) The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38(3):635–647PubMedCrossRefGoogle Scholar
  8. 8.
    Emerich DF, Thanos CG (2003) Nanotechnology and medicine. Expert Opin Biol Ther 3:655–663PubMedCrossRefGoogle Scholar
  9. 9.
    What is nanotechnology? National Nanotechnology Initiative. http://nano.gov/nanotech-101/what/definition. Accessed 5 Apr 2014
  10. 10.
    Fakruddin M, Hossain Z, Afroz H (2012) Prospects and applications of nanobiotechnology: a medical perspective. J Nanobiotechnology 10:31PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Moghimi SM, Hunter AC, Murray JC (2005) Nanomedicine: current status and future prospects. FASEB J 19:311–330PubMedCrossRefGoogle Scholar
  12. 12.
    Aizenberg J, Weaver JC, Thanawala MS, Sundar VC, Morse DE, Fratzl P (2005) Skeleton of Euplectella sp.: structural hierarchy from the nanoscale to the macroscale. Science 309(5732):275–278PubMedCrossRefGoogle Scholar
  13. 13.
    Fantner GE, Hassenkam T, Kindt JH, Weaver JC, Birkedal H, Pechenik L et al (2005) Sacrificial bonds and hidden length dissipate energy as mineralized fibrils separate during bone fracture. Nat Mater 4(8):612–616PubMedCrossRefGoogle Scholar
  14. 14.
    Chen PY, Lin AY, Lin YS, Seki Y, Stokes AG, Peyras J et al (2008) Structure and mechanical properties of selected biological materials. J Mech Behav Biomed Mater 1(3):208–226PubMedCrossRefGoogle Scholar
  15. 15.
    Hang F, Barber AH (2011) Nano-mechanical properties of individual mineralized collagen fibrils from bone tissue. J R Soc Interface 8(57):500–505PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Landis WJ, Silver FH (2009) Mineral deposition in the extracellular matrices of vertebrate tissues: identification of possible apatite nucleation sites on type I collagen. Cells Tissues Organs 189(1–4):20–24PubMedCrossRefGoogle Scholar
  17. 17.
    Wiesmann HP, Meyer U, Plate U, Höhling HJ (2005) Aspects of collagen mineralization in hard tissue formation. Int Rev Cytol 242:121–156PubMedCrossRefGoogle Scholar
  18. 18.
    Gupta HS, Wagermaier W, Zickler GA, Raz-Ben Aroush D, Funari SS, Roschger P et al (2005) Nanoscale deformation mechanisms in bone. Nano Lett 5(10):2108–2111PubMedCrossRefGoogle Scholar
  19. 19.
    Garg T, Singh O, Arora S, Murthy R (2012) Scaffold: a novel carrier for cell and drug delivery. Crit Rev Ther Drug Carrier Syst 29(1):1–63PubMedCrossRefGoogle Scholar
  20. 20.
    Ikeda R, Fujioka H, Nagura I, Kokubu T, Toyokawa N, Inui A et al (2009) The effect of porosity and mechanical property of a synthetic polymer scaffold on repair of osteochondral defects. Int Orthop 33(3):821–828PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Zimmerman EA, Barth HD, Ritchie RO (2012) On the multiscale origins of fracture resistance in human bone and its biological degradation. JOM 64:486–493CrossRefGoogle Scholar
  22. 22.
    Dzenis Y (2008) Materials science. Structural nanocomposites. Science 319(5862):419–420PubMedCrossRefGoogle Scholar
  23. 23.
    Launey ME, Munch E, Alsem DH, Barth HB, Saiz E, Tomsia AP et al (2009) Designing highly toughened hybrid composites through nature-inspired hierarchical complexity. Acta Mater 57:2919–2932CrossRefGoogle Scholar
  24. 24.
    Ritchie RO (2008) The quest for stronger, tougher materials. Science 320:448PubMedCrossRefGoogle Scholar
  25. 25.
    Saiz E, Zimmermann EA, Lee JS, Wegst UG, Tomsia AP (2013) Perspectives on the role of nanotechnology in bone tissue engineering. Dent Mater 29(1):103–115PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Chevalier J, Gremillard L, Deville S (2007) Low-temperature degradation of zirconia and implications for biomedical implants. Annu Rev Mater Res 37:1–32CrossRefGoogle Scholar
  27. 27.
    Zhang ZG, Li ZH, Mao XZ, Wang WC (2011) Advances in bone repair with nanobiomaterials: mini-review. Cytotechnology 63(5):437–443PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Ma PX, Zhang R, Xiao G, Franceschi R (2001) Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds. J Biomed Mater Res 54(2):284–293PubMedCrossRefGoogle Scholar
  29. 29.
    Qian J, Xu W, Yong X, Jin X, Zhang W (2014) Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering. Mater Sci Eng C Mater Biol Appl 36:95–101PubMedCrossRefGoogle Scholar
  30. 30.
    Karp JM, Langer R (2007) Development and therapeutic applications of advanced biomaterials. Curr Opin Biotechnol 18(5):454–459PubMedCrossRefGoogle Scholar
  31. 31.
    Le X, Poinern GE, Ali N, Berry CM, Fawcett D (2013) Engineering a biocompatible scaffold with either micrometre or nanometre scale surface topography for promoting protein adsorption and cellular response. Int J Biomater 2013:782549. doi: 10.1155/2013/782549 PubMedCentralPubMedGoogle Scholar
  32. 32.
    Curtis AS, Gadegaard N, Dalby MJ, Riehle MO, Wilkinson CD, Aitchison G (2004) Cells react to nanoscale order and symmetry in their surroundings. IEEE Trans Nanobiosci 3(1):61–65CrossRefGoogle Scholar
  33. 33.
    Biggs MJ, Richards RG, Gadegaard N, McMurray RJ, Affrossman S, Wilkinson CD et al (2009) Interactions with nanoscale topography: adhesion quantification and signal transduction in cells of osteogenic and multipotent lineage. J Biomed Mater Res A 91(1):195–208PubMedCrossRefGoogle Scholar
  34. 34.
    Sniadecki NJ, Desai RA, Ruiz SA, Chen CS (2006) Nanotechnology for cell-substrate interactions. Ann Biomed Eng 34(1):59–74PubMedCrossRefGoogle Scholar
  35. 35.
    Nielson R, Kaehr B, Shear JB (2009) Microreplication and design of biological architectures using dynamic-mask multiphoton lithography. Small 5(1):120–125PubMedCrossRefGoogle Scholar
  36. 36.
    Hu X, Park SH, Gil ES, Xia XX, Weiss AS, Kaplan DL (2011) The influence of elasticity and surface roughness on myogenic and osteogenic differentiation of cells on silk-elastin. Biomaterials 32(34):8979–8989PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Lamers E, Walboomers XF, Domanski M, Prodanov L, Melis J, Luttge R et al (2012) In vitro and in vivo evaluation of the inflammatory response to nanoscale grooved substrates. Nanomedicine 8(3):308–317PubMedCrossRefGoogle Scholar
  38. 38.
    Webster TJ, Ejiofor JU (2004) Increased osteoblast adhesion on nanophase metals: Ti, Ti6Al4V, and CoCrMo. Biomaterials 25(19):4731–4739PubMedCrossRefGoogle Scholar
  39. 39.
    Tran N, Webster TJ (2009) Nanotechnology for bone materials. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(3):336–351PubMedCrossRefGoogle Scholar
  40. 40.
    Wang J, Yu X (2010) Preparation, characterization and in vitro analysis of novel structured nanofibrous scaffolds for bone tissue engineering. Acta Biomater 6(8):3004–3012PubMedCrossRefGoogle Scholar
  41. 41.
    Hao W, Dong J, Jiang M, Wu J, Cui F, Zhou D (2010) Enhanced bone formation in large segmental radial defects by combining adipose-derived stem cells expressing bone morphogenetic protein 2 with nHA/RHLC/PLA scaffold. Int Orthop 34(8):1341–1349PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Khang D, Carpenter J, Chun YW, Pareta R, Webster TJ (2010) Nanotechnology for regenerative medicine. Biomed Microdevices 12(4):575–587PubMedCrossRefGoogle Scholar
  43. 43.
    Laurencin CT, Kumbar SG, Nukavarapu SP (2009) Nanotechnology and orthopedics: a personal perspective. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(1):6–10PubMedCrossRefGoogle Scholar
  44. 44.
    Mafi P, Hindocha S, Mafi R, Khan WS (2012) Evaluation of biological protein-based collagen scaffolds in cartilage and musculoskeletal tissue engineering–a systematic review of the literature. Curr Stem Cell Res Ther 7(4):302–309PubMedCrossRefGoogle Scholar
  45. 45.
    Li WJ, Cooper JA Jr, Mauck RL, Tuan RS (2006) Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications. Acta Biomater 2(4):377–385PubMedCrossRefGoogle Scholar
  46. 46.
    Venugopal JR, Low S, Choon AT, Kumar AB, Ramakrishna S (2008) Nanobioengineered electrospun composite nanofibers and osteoblasts for bone regeneration. Artif Organs 32(5):388–397PubMedCrossRefGoogle Scholar
  47. 47.
    Xiao X, Liu R, Huang Q (2008) Preparation and characterization of nano-hydroxyapatite/polymer composite scaffolds. J Mater Sci Mater Med 19(11):3429–3435PubMedCrossRefGoogle Scholar
  48. 48.
    Price RL, Ellison K, Haberstroh KM, Webster TJ (2004) Nanometer surface roughness increases select osteoblast adhesion on carbon nanofiber compacts. J Biomed Mater Res A 70(1):129–138PubMedCrossRefGoogle Scholar
  49. 49.
    Bhattacharya M, Wutticharoenmongkol-Thitiwongsawet P, Hamamoto DT, Lee D, Cui T, Prasad HS, Ahmad M (2011) Bone formation on carbon nanotube composite. J Biomed Mater Res A 96(1):75–82PubMedCrossRefGoogle Scholar
  50. 50.
    Horii A, Wang X, Gelain F, Zhang S (2007) Biological designer self-assembling peptide nanofiber scaffolds significantly enhance osteoblast proliferation, differentiation and 3-D migration. PLoS One 2(2):e190PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Marí-Buyé N, Luque T, Navajas D, Semino CE (2013) Development of a three-dimensional bone-like construct in a soft self-assembling peptide matrix. Tissue Eng Part A 19(7–8):870–881PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Misawa H, Kobayashi N, Soto-Gutierrez A, Chen Y, Yoshida A, Rivas-Carrillo JD et al (2006) PuraMatrix facilitates bone regeneration in bone defects of calvaria in mice. Cell Transplant 15(10):903–910PubMedCrossRefGoogle Scholar
  53. 53.
    Gu W, Wu C, Chen J, Xiao Y (2013) Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration. Int J Nanomedicine 8:2305–2317PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Zhang S, Uludağ H (2009) Nanoparticulate systems for growth factor delivery. Pharm Res 26:1561–1580PubMedCrossRefGoogle Scholar
  55. 55.
    Hosseinkhani H, Hosseinkhani M, Khademhosseini A, Kobayashi H (2007) Bone regeneration through controlled release of bone morphogenetic protein-2 from 3-D tissue engineered nano-scaffold. J Control Release 117(3):380–386PubMedCrossRefGoogle Scholar
  56. 56.
    Tabata T, Takei Y (2004) Morphogens, their identification and regulation. Development 131(4):703–712PubMedCrossRefGoogle Scholar
  57. 57.
    Phillippi JA, Miller E, Weiss L, Huard J, Waggoner A, Campbell P (2008) Microenvironments engineered by inkjet bioprinting spatially direct adult stem cells toward muscle- and bone-like subpopulations. Stem Cells 26(1):127–134PubMedCrossRefGoogle Scholar
  58. 58.
    Cooper GM, Miller ED, Decesare GE, Usas A, Lensie EL, Bykowski MR et al (2010) Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation. Tissue Eng Part A 16(5):1749–1759PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Domachuk P, Tsioris K, Omenetto FG, Kaplan DL (2010) Bio-microfluidics: biomaterials and biomimetic designs. Adv Mater 22(2):249–260PubMedCrossRefGoogle Scholar
  60. 60.
    Wang X, Wenk E, Zhang X, Meinel L, Vunjak-Novakovic G, Kaplan DL (2009) Growth factor gradients via microsphere delivery in biopolymer scaffolds for osteochondral tissue engineering. J Control Release 134(2):81–90PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Pavlukhina S, Sukhishvili S (2011) Polymer assemblies for controlled delivery of bioactive molecules from surfaces. Adv Drug Deliv Rev 63(9):822–836PubMedCrossRefGoogle Scholar
  62. 62.
    Shah NJ, Macdonald ML, Beben YM, Padera RF, Samuel RE, Hammond PT (2011) Tunable dual growth factor delivery from polyelectrolyte multilayer films. Biomaterials 32(26):6183–6193PubMedCentralPubMedGoogle Scholar

Copyright information

© SICOT aisbl 2014

Authors and Affiliations

  • Nadomir Gusić
    • 1
  • Alan Ivković
    • 2
    • 3
    • 4
    Email author
  • John VaFaye
    • 5
  • Andreja Vukasović
    • 6
  • Jana Ivković
    • 2
  • Damir Hudetz
    • 3
    • 4
  • Saša Janković
    • 3
  1. 1.Department of TraumatologyGeneral Hospital PulaPulaCroatia
  2. 2.Department of BiotechnologyUniversity of RijekaRijekaCroatia
  3. 3.Department of Orthopaedic SurgeryUniversity Hospital Sveti DuhZagrebCroatia
  4. 4.Department of Orthopaedic SurgerySt. Catherine’s HospitalZabokCroatia
  5. 5.Department of Orthopaedic Surgery, Care UK Northeast London NHS Treatment CentreKing George HospitalIlfordUK
  6. 6.Department of Histology and Embryology, School of MedicineUniversity of ZagrebZagrebCroatia

Personalised recommendations