, Volume 95, Issue 2, pp 69–80 | Cite as

Electrospun scaffolds for bone tissue engineering

  • Alberto Di Martino
  • Liliana Liverani
  • Alberto Rainer
  • Giuseppe Salvatore
  • Marcella Trombetta
  • Vincenzo Denaro


Tissue engineering aims to regenerate native tissues and will represent the alternative choice of standard surgery for different kind of tissue damages. The fundamental basis of tissue engineering is the appropriate selection of scaffolds and their morphological, mechanical, chemical, and biomimetic properties, closely related to cell lines that will be seeded therein. The aim of this review is to summarize and report the innovative scientific contributions published in the field of orthopedic tissue engineering, in particular about bone tissue engineering. We have focused our attention on the electrospinning technique, as a scaffold fabrication method. Electrospun materials are being evaluated as scaffolds for bone tissue engineering, and the results of all these studies clearly indicate that they represent suitable potential substrates for cell-based technologies.


Bone tissue engineering Electrospinning Nanofibers Scaffold Stem cells 


  1. 1.
    Langer R, Vacanti J (1993) Tissue engineering. Science 260:920–926PubMedCrossRefGoogle Scholar
  2. 2.
    Bhardwaj N, Kundu SC (2010) Electrospinning: a fascinating fiber fabrication technique. Biotechnol Adv 28:325–347Google Scholar
  3. 3.
    Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK (2002) Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res 60:613–621PubMedCrossRefGoogle Scholar
  4. 4.
    Friess W (1998) Collagen–biomaterial for drug delivery. Eur J Pharm Biopharm 45:113–136PubMedCrossRefGoogle Scholar
  5. 5.
    Di Martino A, Silber JS,Vaccaro AR (2006) Bone graft alternatives in spinal surgery. In: Gunzburg R, Szpalski M (eds) Spondylosis, spondylolysthesis and degenerative spondylolisthesis. Lippincott Williams and Wilkins, Philadelphia, pp 237–255Google Scholar
  6. 6.
    Ehrbar M, Lütolf MP, Rizzi SC, Hubbell JA, Weber FE (2008) Artificial extracellular matrices for bone tissue engineering. Bone 42:S72CrossRefGoogle Scholar
  7. 7.
    Huang Z-M, Zhang YZ, Kotaki M, Ramakrishna S (2003) A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos Sci Technol 63:2223–2253CrossRefGoogle Scholar
  8. 8.
    Liao S, Chan C, Ramakrishna S (2010) Electrospun nanofibers: work for medicine? Front Mater Sci China 4:29–33CrossRefGoogle Scholar
  9. 9.
    Lu P, Ding B (2008) Applications of electrospun fibers. Recent Pat Nanotechnol 2:169–182PubMedCrossRefGoogle Scholar
  10. 10.
    Secasanu VP, Giardina CK, Wang Y (2009) A novel electrospinning target to improve the yield of uniaxially aligned fibers. Biotechnol Prog 25:1169–1175PubMedCrossRefGoogle Scholar
  11. 11.
    Murugan R, Ramakrishna S (2006) Nano-featured scaffolds for tissue engineering: a review of spinning methodologies. Tissue Eng 12:435–447PubMedCrossRefGoogle Scholar
  12. 12.
    Park SA, Park K, Yoon H, Son J, Min T, Kim GH (2007) Apparatus for preparing electrospun nanofibers: designing an electrospinning process for nanofiber fabrication. Polym Int 56:1361–1366CrossRefGoogle Scholar
  13. 13.
    Agarwal S, Wendorff JH, Greiner A (2009) Progress in the field of electrospinning for tissue engineering applications. Adv Mat 21:3343–3351CrossRefGoogle Scholar
  14. 14.
    Zhu Y, Cao Y, Pan J, Liu Y (2010) Macro-alignment of electrospun fibers for vascular tissue engineering. J Biomed Mater Res B Appl Biomater 92:508–516PubMedGoogle Scholar
  15. 15.
    Jayasinghe SN, Irvine S, McEwan JR (2007) Cell electrospinning highly concentrated cellular suspensions containing primary living organisms into cell-bearing threads and scaffolds. Nanomedicine (Lond) 2:555–567CrossRefGoogle Scholar
  16. 16.
    Stankus JJ, Guan J, Fujimoto K, Wagner WR (2006) Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix. Biomaterials 27:735–744PubMedCrossRefGoogle Scholar
  17. 17.
    Kalra V, Lee JH, Park JH, Marquez M, Joo YL (2009) Confined assembly of asymmetric block-copolymer nanofibers via multiaxial jet electrospinning. Small 5:2323–2332PubMedCrossRefGoogle Scholar
  18. 18.
    Kim GH, Min T, Park SA, Kim WD (2008) Coaxially electrospun micro/nanofibrous poly(epsilon-caprolactone)/eggshell-protein scaffold. Bioinspir Biomim 3:16006CrossRefGoogle Scholar
  19. 19.
    Spivak AF, Dzenis YA, Reneker DH (2000) A model of steady state jet in the electrospinning process. Mech Res Commun 27:37–42Google Scholar
  20. 20.
    Helgeson ME, Grammatikos KN, Deitzel JM, Wagner NJ (2008) Theory and kinematic measurements of the mechanics of stable electrospun polymer jets. Polymer 49:2924–2936CrossRefGoogle Scholar
  21. 21.
    Xu L (2009) A mathematical model for electrospinning process under coupled field forces. Chaos Solitons Fractals 42:1463–1465CrossRefGoogle Scholar
  22. 22.
    Sill TJ, von Recum HA (2008) Electrospinning: applications in drug delivery and tissue engineering. Biomaterials 29:1989–2006PubMedCrossRefGoogle Scholar
  23. 23.
    Ramakrishna S, Fujihara K, Teo WE, Lim CT, Ma Z (2005) An introduction to electrospinning and nanofibers. World Scientific Publishing Co. Pte. Ltd, SingaporeCrossRefGoogle Scholar
  24. 24.
    Flemming RG, Murphy CJ, Abrams GA, Goodman SL, Nealey PF (1999) Effects of synthetic micro- and nano-structured surfaces on cell behavior. Biomaterials 20:573–588PubMedCrossRefGoogle Scholar
  25. 25.
    Green AM, Jansen JA, JPCMvd Waerden, Recum AFV (1994) Fibroblast response to microtextured silicone surfaces: texture orientation into or out of the surface. J Biomed Mat Res 28:647–653CrossRefGoogle Scholar
  26. 26.
    Sharma B, Elisseeff JH (2004) Engineering structurally organized cartilage and bone tissues. Ann Biomed Eng 32:148–159PubMedCrossRefGoogle Scholar
  27. 27.
    Liu X, Ma PX (2004) Polymeric scaffolds for bone tissue engineering. Ann Biomed Eng 32:477–486PubMedCrossRefGoogle Scholar
  28. 28.
    Jang JH, Castano O, Kim HW (2009) Electrospun materials as potential platforms for bone tissue engineering. Adv Drug Deliv Rev 61:1065–1083PubMedCrossRefGoogle Scholar
  29. 29.
    Webster TJ (2007) Nanotechnology for the regeneration of hard and soft tissues. World Scientific, HackensackCrossRefGoogle Scholar
  30. 30.
    Vaes G (1988) Cellular biology and biochemical mechanism of bone resorption. A review of recent developments on the formation, activation, and mode of action of osteoclasts. Clin Orthop Relat Res 239–271Google Scholar
  31. 31.
    Trippel SB (1998) Potential role of insulinlike growth factors in fracture healing. Clin Orthop Relat Res S301–313Google Scholar
  32. 32.
    Ma PX, Elisseeff JH (2005) Scaffolding in tissue engineering. Taylor&Francis, Boca RatonCrossRefGoogle Scholar
  33. 33.
    Ma Z, Kotaki M, Inai R, Ramakrishna S (2005) Potential of Nanofiber Matrix as Tissue-Engineering Scaffolds. Tissue Eng 11:101–109Google Scholar
  34. 34.
    Albrektsson T, Johansson C (2001) Osteoinduction, osteoconduction and osseointegration. Eur Spine J 10:S96–S101PubMedCrossRefGoogle Scholar
  35. 35.
    Haynesworth SE, Goshima J, Goldberg VM, Caplan AI (1992) Characterization of cells with osteogenic potential from human marrow. Bone 13:81–88PubMedCrossRefGoogle Scholar
  36. 36.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  37. 37.
    Young RG, Butler DL, Weber W, Caplan AI, Gordon SL, Fink DJ (1998) Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res 16:406–413PubMedCrossRefGoogle Scholar
  38. 38.
    Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, Maini RN (2000) Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2:477–488PubMedCrossRefGoogle Scholar
  39. 39.
    Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S (2005) Circulating osteoblast-lineage cells in humans. N Engl J Med 352:1959–1966PubMedCrossRefGoogle Scholar
  40. 40.
    Eghbali-Fatourechi GZ, Modder UI, Charatcharoenwitthaya N, Sanyal A, Undale AH, Clowes JA, Tarara JE, Khosla S (2007) Characterization of circulating osteoblast lineage cells in humans. Bone 40:1370–1377PubMedCrossRefGoogle Scholar
  41. 41.
    Bieback K, Kern S, Kluter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cell 22:625–634CrossRefGoogle Scholar
  42. 42.
    Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228PubMedCrossRefGoogle Scholar
  43. 43.
    Teo WE, He W, Ramakrishna S (2006) Electrospun scaffold tailored for tissue-specific extracellular matrix. Biotechnol J 1:918–929PubMedCrossRefGoogle Scholar
  44. 44.
    Sokolsky-Papkov M, Agashi K, Olaye A, Shakesheff K, Domb AJ (2007) Polymer carriers for drug delivery in tissue engineering. Adv Drug Deliv Rev 59:187–206PubMedCrossRefGoogle Scholar
  45. 45.
    Ma Z, Ramakrishna S (2004) Nanostructured extracellular matrix. Encycl Nanosci Nanotechnol 7:641–655Google Scholar
  46. 46.
    Nelson WJ (2008) Regulation of cell–cell adhesion by the cadherin–catenin complex. Biochem Soc Trans 036:149–155CrossRefGoogle Scholar
  47. 47.
    Venugopal J, Prabhakaran MP, Low S, Choon AT, Zhang YZ, Deepika G, Ramakrishna S (2008) Nanotechnology for nanomedicine and delivery of drugs. Curr Pharm Des 14:2184–2200PubMedCrossRefGoogle Scholar
  48. 48.
    Burg KJL, Porter S, Kellam JF (2000) Biomaterial developments for bone tissue engineering. Biomaterials 21:2347–2359PubMedCrossRefGoogle Scholar
  49. 49.
    Yoshimoto H, Shin YM, Terai H, Vacanti JP (2003) A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 24:2077–2082PubMedCrossRefGoogle Scholar
  50. 50.
    Shin M, Yoshimoto H, Vacanti JP (2004) In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold. Tissue Eng 10:33–41PubMedCrossRefGoogle Scholar
  51. 51.
    Binulal NS, Deepthy M, Selvamurugan N, Shalumon KT, Suja S, Mony U, Jayakumar R, Nair SV (2010) Role of nanofibrous poly(caprolactone) scaffolds in human mesenchymal stem cell attachment and spreading for in vitro bone tissue engineering—response to osteogenic regulators. Tissue Eng Part A 16:393–404PubMedCrossRefGoogle Scholar
  52. 52.
    Ruckh TT, Kumar K, Kipper MJ, Popat KC (2010) Osteogenic differentiation of bone marrow stromal cells on poly([epsilon]-caprolactone) nanofiber scaffolds. Acta Biomat 6:2949–2959Google Scholar
  53. 53.
    Badami AS, Kreke MR, Thompson MS, Riffle JS, Goldstein AS (2006) Effect of fiber diameter on spreading, proliferation, and differentiation of osteoblastic cells on electrospun poly(lactic acid) substrates. Biomaterials 27:596–606PubMedCrossRefGoogle Scholar
  54. 54.
    Shih Y-RV, Chen C-N, Tsai S-W, Wang YJ, Lee OK (2006) Growth of mesenchymal stem cells on electrospun type i collagen nanofibers. Stem Cell 24:2391–2397CrossRefGoogle Scholar
  55. 55.
    Zeugolis DI, Khew ST, Yew ESY, Ekaputra AK, Tong YW, Yung L-YL, Hutmacher DW, Sheppard C, Raghunath M (2008) Electro-spinning of pure collagen nano-fibres–Just an expensive way to make gelatin? Biomaterials 29:2293–2305PubMedCrossRefGoogle Scholar
  56. 56.
    Zeugolis DI, Li B, Lareu RR, Chan CK, Raghunath M (2008) Collagen solubility testing, a quality assurance step for reproducible electro-spun nano-fibre fabrication. A technical note. J Biomat Sci Polym Ed 19:1307–1317CrossRefGoogle Scholar
  57. 57.
    Barnes CP, Pemble CW, Brand DD, Simpson DG, Bowlin GL (2007) Cross-linking electrospun type II collagen tissue engineering scaffolds with carbodiimide in ethanol. Tissue Eng 13:1593–1605PubMedCrossRefGoogle Scholar
  58. 58.
    Meinel AJ, Kubow KE, Klotzsch E, Garcia-Fuentes M, Smith ML, Vogel V, Merkle HP, Meinel L (2009) Optimization strategies for electrospun silk fibroin tissue engineering scaffolds. Biomaterials 30:3058–3067PubMedCrossRefGoogle Scholar
  59. 59.
    Jin HJ, Chen J, Karageorgiou V, Altman GH, Kaplan DL (2004) Human bone marrow stromal cell responses on electrospun silk fibroin mats. Biomaterials 25:1039–1047PubMedCrossRefGoogle Scholar
  60. 60.
    Meechaisue C, Wutticharoenmongkol P, Waraput R, Huangjing T, Ketbumrung N, Pavasant P, Supaphol P (2007) Preparation of electrospun silk fibroin fiber mats as bone scaffolds: a preliminary study. Biomed Mater 2:181–188PubMedCrossRefGoogle Scholar
  61. 61.
    Park SY, Ki CS, Park YH, Jung HM, Woo KM,Kim HJ (2010) Electrospun silk fibroin scaffolds with macropores for bone regeneration: an in vitro and in vivo study. Tissue Eng Part A 16:1271–1279Google Scholar
  62. 62.
    Di Martino A, Sittinger M, Risbud MV (2005) Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials 26:5983–5990PubMedCrossRefGoogle Scholar
  63. 63.
    Ohkawa K, Cha D, Kim H, Nishida A, Yamamoto H (2004) Electrospinning of chitosan. Macromol Rapid Commun 25:1600–1605CrossRefGoogle Scholar
  64. 64.
    Shin S-Y, Park H-N, Kim K-H, Lee M-H, Choi YS, Park Y-J, Lee Y-M, Ku Y, Rhyu I-C, Han S-B, Lee S-J, Chung C-P (2005) Biological evaluation of chitosan nanofiber membrane for guided bone regeneration. J Periodontol 76:1778–1784PubMedCrossRefGoogle Scholar
  65. 65.
    Ekaputra AK, Zhou Y, Cool SM, Hutmacher DW (2009) Composite electrospun scaffolds for engineering tubular bone grafts. Tissue Eng Part A 15:3779–3788PubMedCrossRefGoogle Scholar
  66. 66.
    Jose MV, Thomas V, Dean DR, Nyairo E (2009) Fabrication and characterization of aligned nanofibrous PLGA/collagen blends as bone tissue scaffolds. Polymer 50:3778–3785CrossRefGoogle Scholar
  67. 67.
    Liao S, Murugan R, Chan CK, Ramakrishna S (2008) Processing nanoengineered scaffolds through electrospinning and mineralization suitable for biomimetic bone tissue engineering. J Mech Behav Biomed Mater 1:252–260PubMedCrossRefGoogle Scholar
  68. 68.
    Olszta MJ, Cheng X, Jee SS, Kumar R, Kim Y-Y, Kaufman MJ, Douglas EP, Gower LB (2007) Bone structure and formation: a new perspective. Mat SciEng R Rep 58:77–116CrossRefGoogle Scholar
  69. 69.
    Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27:3413–3431PubMedCrossRefGoogle Scholar
  70. 70.
    Ko EK, Jeong SI, Rim NG, Lee YM, Shin H, Lee B-K (2008) In vitro osteogenic differentiation of human mesenchymal stem cells and in vivo bone formation in composite nanofiber meshes. Tissue Eng Part A 14:2105–2119PubMedCrossRefGoogle Scholar
  71. 71.
    Chuenjitkuntaworn B, Supaphol P, Pavasant P, Damrongsri D (2010) Electrospun polyL-lactic acidhydroxyapatite composite fibrous scaffolds for bone tissue engineering. Polym Int 59:227–235Google Scholar
  72. 72.
    Zhang H, Chen Z (2010) Fabrication and characterization of electrospun PLGA/MWNTs/hydroxyapatite biocomposite scaffolds for bone tissue engineering. J Bioact Compat Polym 0883911509359486Google Scholar
  73. 73.
    Zhang Y, Venugopal JR, El-Turki A, Ramakrishna S, Su B, Lim CT (2008) Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering. Biomaterials 29:4314–4322PubMedCrossRefGoogle Scholar
  74. 74.
    Zhang Y, Jayarama Reddy V, Wong SY, Li X, Su B, Ramakrishna S, Lim CT (2010) Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan. Tissue Eng Part A 16:1949–1960Google Scholar
  75. 75.
    Prabhakaran MP, Venugopal J, Ramakrishna S (2009) Electrospun nanostructured scaffolds for bone tissue engineering. Acta Biomater 5:2884–2893PubMedCrossRefGoogle Scholar
  76. 76.
    Kim H-W, Song J-H, Kim H-E (2006) Bioactive glass nanofiber-collagen nanocomposite as a novel bone regeneration matrix. J Biomed Mat Res Part A 79A:698–705CrossRefGoogle Scholar
  77. 77.
    Kim H-W, Lee H-H, Chun G-S (2008) Bioactivity and osteoblast responses of novel biomedical nanocomposites of bioactive glass nanofiber filled poly(lactic acid). J Biomed Mat Res Part A 85A:651–663CrossRefGoogle Scholar
  78. 78.
    Ren L, Wang J, Yang F-Y, Wang L, Wang D, Wang T-X, Tian M-M (2010) Fabrication of gelatin-siloxane fibrous mats via sol-gel and electrospinning procedure and its application for bone tissue engineering. Mat Sci Eng C 30:437–444CrossRefGoogle Scholar
  79. 79.
    Li C, Vepari C, Jin H-J, Kim HJ, Kaplan DL (2006) Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials 27:3115–3124PubMedCrossRefGoogle Scholar
  80. 80.
    Lee E-J, Teng S-H, Jang T-S, Wang P, Yook S-W, Kim H-E, Koh Y-H (2010) Nanostructured poly([epsilon]-caprolactone)-silica xerogel fibrous membrane for guided bone regeneration. Acta Biomat 6:3557–3565Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Alberto Di Martino
    • 1
  • Liliana Liverani
    • 2
  • Alberto Rainer
    • 2
  • Giuseppe Salvatore
    • 1
  • Marcella Trombetta
    • 2
  • Vincenzo Denaro
    • 1
  1. 1.Department of Orthopaedics and Trauma SurgeryUniversity Campus Bio-Medico of RomeRomeItaly
  2. 2.CIR - Tissue Engineering LaboratoryUniversity Campus Bio-Medico of RomeRomeItaly

Personalised recommendations