Journal of Materials Science

, Volume 50, Issue 12, pp 4174–4186 | Cite as

Hierarchically decorated electrospun poly(\( \varepsilon \)-caprolactone)/nanohydroxyapatite composite nanofibers for bone tissue engineering

Original Paper


Bone is a nanocomposite comprised of two main components, nanohydroxyapatite (nHA) and Type I collagen. The aim of this study is to mimic the nanotopography of collagen fibrils in bone tissue and to modulate their cellular functions by nanoscale stimulation. Three-dimensional structures consisting of electrospun poly(\( \varepsilon \)-caprolactone) (PCL) and PCL/nHA composite nanofibers decorated by periodically spaced PCL crystal lamellae (shish–kebab structure) were created. It was found that the hierarchically decorated nanostructure not only enhanced the mechanical properties of the scaffolds but also changed the surface wettability behavior of the scaffolds. The enhanced surface wettability facilitated biomimetic mineralization through apatite deposition when exposed to simulated body fluids (SBF). MG-63, an osteosarcoma cell line which behaves similarly to osteoblasts, was used to study the cellular response to the scaffolds. Data suggest kebab crystal nanotopography facilitating cell attachment and proliferation. Functional assays, which quantify alkaline phosphatase (ALP) and calcium expression, revealed increased ALP activity and increased calcium expression on decorated nanofibers. In addition, compared with other scaffolds, the cells on PCL/nHA nanofibrous shish–kebab-structured scaffolds showed obvious extended pseudopodia of the filaments in the cytoskeleton study, demonstrating better interactions between cells and scaffolds.


Simulated Body Fluid Water Contact Angle Bone Tissue Engineering Composite Nanofibers Composite Scaffold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge the support of the Wisconsin Institute for Discovery (WID), the China Scholarship Council, the financial support of the National Nature Science Foundation of China (No. 51073061, No. 21174044), the Guangdong Nature Science Foundation (No. S2013020013855, No. 9151064101000066), and the National Basic Research Development Program 973 (No. 2012CB025902) in China.


  1. 1.
    Weiner S, Wagner HD (1998) The material bone: structure mechanical function relations. Annu Rev Mater Sci 28:271–298CrossRefGoogle Scholar
  2. 2.
    Weiner S, Traub W (1986) Organization of hydroxyapatite crystals within collagen fibrils. FEBS Lett 206:262–266CrossRefGoogle Scholar
  3. 3.
    Fratzl P, Weinkamer R (2007) Nature’s hierarchical materials. Prog Mater Sci 52:1263–1334CrossRefGoogle Scholar
  4. 4.
    Azami M, Moosavifar MJ, Baheiraei N, Moztarzadeh F, Ai J (2012) Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering via mineralization of gelatin hydrogel and study of mineral transformation in simulated body fluid. J Biomed Mater Res A 100A:1347–1355CrossRefGoogle Scholar
  5. 5.
    Chen JL, Chu B, Hsiao BS (2006) Mineralization of hydroxyapatite in electrospun nanofibrous poly(l-lactic acid) scaffolds. J Biomed Mater Res A 79A:307–317CrossRefGoogle Scholar
  6. 6.
    Nguyen TH, Bao TQ, Park I, Lee BT (2013) A novel fibrous scaffold composed of electrospun porous poly(epsilon-caprolactone) fibers for bone tissue engineering. J Biomater Appl 28:514–528CrossRefGoogle Scholar
  7. 7.
    Jegal SH, Park JH, Kim JH et al (2011) Functional composite nanofibers of poly(lactide-co-caprolactone) containing gelatin-apatite bone mimetic precipitate for bone regeneration. Acta Biomater 7:1609–1617CrossRefGoogle Scholar
  8. 8.
    Phipps MC, Clem WC, Grunda JM, Dines GA, Bellis SL (2012) Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. Biomaterials 33:524–534CrossRefGoogle Scholar
  9. 9.
    Xie JW, Li XR, Lipner J et al (2010) “Aligned-to-random” nanofiber scaffolds for mimicking the structure of the tendon-to-bone insertion site. Nanoscale 2:923–926CrossRefGoogle Scholar
  10. 10.
    Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK (2002) Electrospun nanofibrous structure: a novel scaffold for tissue engineering. J Biomed Mater Res 60:613–621CrossRefGoogle Scholar
  11. 11.
    Wutticharoenmongkol P, Sanchavanakit N, Pavasant P, Supaphol P (2006) Preparation and characterization of novel bone scaffolds based on electrospun polycaprolactone fibers filled with nanoparticles. Macromol Biosci 6:70–77CrossRefGoogle Scholar
  12. 12.
    Venugopal J, Low S, Choon AT, Kumar AB, Ramakrishna S (2008) Electrospun-modified nanofibrous scaffolds for the mineralization of osteoblast cells. J Biomed Mater Res A 85A:408–417CrossRefGoogle Scholar
  13. 13.
    Puppi D, Piras AM, Chiellini F et al (2011) Optimized electro- and wet-spinning techniques for the production of polymeric fibrous scaffolds loaded with bisphosphonate and hydroxyapatite. J Tissue Eng Regen Med 5:253–263CrossRefGoogle Scholar
  14. 14.
    Patlolla A, Arinzeh TL (2014) Evaluating apatite formation and osteogenic activity of electrospun composites for bone tissue engineering. Biotechnol Bioeng 111:1000–1017CrossRefGoogle Scholar
  15. 15.
    Fang M, Goldstein EL, Matich EK, Orr BG, Holl MMB (2013) Type I collagen self-assembly: the roles of substrate and concentration. Langmuir 29:2330–2338CrossRefGoogle Scholar
  16. 16.
    Vetrone F, Variola F, de Oliveira PT et al (2009) Nanoscale oxidative patterning of metallic surfaces to modulate cell activity and fate. Nano Lett 9:659–665CrossRefGoogle Scholar
  17. 17.
    Binsberg F (1966) Orientation-induced nucleation in polymer crystallization. Nature 211:516–517CrossRefGoogle Scholar
  18. 18.
    Pennings AJ, Kiel AM (1965) Fractionation of Polymers by Crystallization from Solution. 3. On Morphology of Fibrillar Polyethylene Crystals Grown in Solution. Kolloid Z Z Polym 205:160–162CrossRefGoogle Scholar
  19. 19.
    Li LY, Li CY, Ni CY (2006) Polymer crystallization-driven, periodic patterning on carbon nanotubes. J Am Chem Soc 128:1692–1699CrossRefGoogle Scholar
  20. 20.
    Chen X, Wang WD, Cheng S, Dong B, Li CY (2013) Mimicking bone nanostructure by combining block copolymer self-assembly and 1D crystal nucleation. ACS Nano 7:8251–8257CrossRefGoogle Scholar
  21. 21.
    Wang XF, Salick MR, Wang XD et al (2013) Poly(epsilon-caprolactone) nanofibers with a self-induced nanohybrid shish-kebab structure mimicking collagen fibrils. Biomacromolecules 14:3557–3569CrossRefGoogle Scholar
  22. 22.
    Kokubo T, Takadama H (2006) How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27:2907–2915CrossRefGoogle Scholar
  23. 23.
    Peng F, Yu XH, Wei M (2011) In vitro cell performance on hydroxyapatite particles/poly(l-lactic acid) nanofibrous scaffolds with an excellent particle along nanofiber orientation. Acta Biomater 7:2585–2592CrossRefGoogle Scholar
  24. 24.
    Rnjak-Kovacina J, Wise SG, Li Z et al (2011) Tailoring the porosity and pore size of electrospun synthetic human elastin scaffolds for dermal tissue engineering. Biomaterials 32:6729–6736CrossRefGoogle Scholar
  25. 25.
    Croisier F, Duwez AS, Jerome C et al (2012) Mechanical testing of electrospun PCL fibers. Acta Biomater 8:218–224CrossRefGoogle Scholar
  26. 26.
    Pirzada T, Arvidson SA, Saquing CD, Shah SS, Khan SA (2012) Hybrid silica-PVA nanofibers via sol-gel electrospinning. Langmuir 28:5834–5844CrossRefGoogle Scholar
  27. 27.
    Zargarian SS, Haddadi-Asl V (2010) A nanofibrous composite scaffold of PCL/hydroxyapatite-chitosan/PVA prepared by electrospinning. Iran Polym J 19:457–468Google Scholar
  28. 28.
    Thomas V, Jagani S, Johnson K et al (2006) Electrospun bioactive nanocomposite scaffolds of polycaprolactone and nanohydroxyapatite for bone tissue engineering. J Nanosci Nanotechnol 6:487–493CrossRefGoogle Scholar
  29. 29.
    Liao GY, Jiang SB, Xia H, Jiang KF (2012) Preparation and characterization of aligned PLLA/PCL/HA composite fibrous membranes. J Macromol Sci A 49:946–951CrossRefGoogle Scholar
  30. 30.
    Wang BB, Li B, Xiong J, Li CY (2008) Hierarchically ordered polymer nanofibers via electrospinning and controlled polymer crystallization. Macromolecules 41:9516–9521CrossRefGoogle Scholar
  31. 31.
    Thomas V, Dean DR, Jose MV, Mathew B, Chowdhury S, Vohra YK (2007) Nanostructured biocomposite scaffolds based on collagen coelectrospun with nanohydroxyapatite. Biomacromolecules 8:631–637CrossRefGoogle Scholar
  32. 32.
    Ning NY, Zhang W, Zhao YS, Luo F, Fu Q (2012) Nanohybrid shish kebab structure and its effect on mechanical properties in poly(l-lactide)/carbon nanotube nanocomposite fibers. Polym Int 61:1634–1639CrossRefGoogle Scholar
  33. 33.
    Hench LL, Wilson J (1993) An introduction to bioceramics. World Scientific, LondonCrossRefGoogle Scholar
  34. 34.
    Yu SC, Hariram KP, Kumar R, Cheang P, Aik KK (2005) In vitro apatite formation and its growth kinetics on hydroxyapatite/polyetheretherketone biocomposites. Biomaterials 26:2343–2352CrossRefGoogle Scholar
  35. 35.
    Rodriguez K, Renneckar S, Gatenholm P (2011) Biomimetic calcium phosphate crystal mineralization on electrospun cellulose-based scaffolds. Acs Appl Mater Interfaces 3:681–689CrossRefGoogle Scholar
  36. 36.
    Yang F, Wolke JGC, Jansen JA (2008) Biomimetic calcium phosphate coating on electrospun poly (epsilon-caprolactone) scaffolds for bone tissue engineering. Chem Eng J 137:154–161CrossRefGoogle Scholar
  37. 37.
    Li MM, Liu WW, Sun JS et al (2013) Culturing primary human osteoblasts on electrospun poly(lactic-co-glycolic acid) and poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering. Acs Appl Mater Interfaces 5:5921–5926CrossRefGoogle Scholar
  38. 38.
    Mi HY, Jing X, Salick MR, Cordie TM, Peng XF, Turng LS (2014) Morphology, mechanical properties, and mineralization of rigid thermoplastic polyurethane/hydroxyapatite scaffolds for bone tissue applications: effects of fabrication approaches and hydroxyapatite size. J Mater Sci 49:2324–2337. doi: 10.1007/s10853-013-7931-3 CrossRefGoogle Scholar
  39. 39.
    Shor L, Guceri S, Wen XJ, Gandhi M, Sun W (2007) Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitro. Biomaterials 28:5291–5297CrossRefGoogle Scholar
  40. 40.
    Lee HJ, Kim SE, Choi HW, Kim CW, Kim KJ, Lee SC (2007) The effect of surface-modified nano-hydroxyapatite on biocompatibility of poly(epsilon-caprolactone)/hydroxyapatite nanocomposites. Eur Polym J 43:1602–1608CrossRefGoogle Scholar
  41. 41.
    Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF (2001) Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation, differentiation and detachment strength. Biomaterials 22:87–96CrossRefGoogle Scholar
  42. 42.
    Golub EE, Harrison G, Taylor AG, Camper S, Shapiro IM (1992) The role of alkaline-phosphatase in cartilage mineralization. Bone Miner 17:273–278CrossRefGoogle Scholar
  43. 43.
    Woo KM, Chen VJ, Ma PX (2003) Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment. J Biomed Mater Res A 67A:531–537CrossRefGoogle Scholar
  44. 44.
    Shi LY, Aid R, Le Visage C, Chew SY (2012) Biomimicking polysaccharide nanofibers promote vascular phenotypes: a potential application for vascular tissue engineering. Macromol Biosci 12:395–401CrossRefGoogle Scholar
  45. 45.
    Jiang X, Cao HQ, Shi LY, Ng SY, Stanton LW, Chew SY (2012) Nanofiber topography and sustained biochemical signaling enhance human mesenchymal stem cell neural commitment. Acta Biomater 8:1290–1302CrossRefGoogle Scholar
  46. 46.
    Kilian KA, Bugarija B, Lahn BT, Mrksich M (2010) Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci USA 107:4872–4877CrossRefGoogle Scholar
  47. 47.
    McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6:483–495CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.The Key Laboratory for Polymer Processing Engineering of Ministry of Education, National Engineering Research Center of Novel Equipment for Polymer ProcessingSouth China University of TechnologyGuangzhouChina
  2. 2.Departments of Orthopedics and Rehabilitation, and Biomedical EngineeringUniversity of Wisconsin–MadisonMadisonUSA
  3. 3.Wisconsin Institutes for DiscoveryUniversity of Wisconsin–MadisonMadisonUSA

Personalised recommendations