Journal of Materials Science

, Volume 49, Issue 5, pp 2324–2337 | Cite as

Morphology, mechanical properties, and mineralization of rigid thermoplastic polyurethane/hydroxyapatite scaffolds for bone tissue applications: effects of fabrication approaches and hydroxyapatite size

  • Hao-Yang Mi
  • Xin Jing
  • Max R. Salick
  • Travis M. Cordie
  • Xiang-Fang Peng
  • Lih-Sheng Turng


Rigid thermoplastic polyurethane (TPU)/hydroxyapatite (HA) scaffolds were prepared with micro HA (mHA) and nano HA (nHA) particles, respectively, via the thermally induced phase separation method. The effects of solvent and co-solvent, addition of sodium chloride (NaCl) porogen, and HA particle size were studied together with the morphology, compressive properties, and mineralization behavior of the scaffolds. Depending on the solvent, co-solvent, or porogen used, different porous structures were produced. In particular, a ladder-like morphology was obtained when dioxane (Di) was used as the solvent, whereas an interconnected porous structure was obtained by using dioxane and deionized water (DiW) as co-solvents. Rectangular pores with interconnected channels on the pore walls were achieved by using NaCl crystals as porogens. The TPU/nHA scaffolds showed stronger compressive properties than the TPU/mHA scaffolds and the pure TPU scaffolds. The scaffolds prepared using dioxane and water as co-solvents exhibit the greatest compressive modulus. Furthermore, TPU scaffolds with nHA particles had the ability to form bone apatite when soaked in simulated body fluid (SBF). After being soaked in SBF for 3 weeks, the weight percentage of formed apatite in the TPU/nHA-DiW scaffold was 9.2 %wt of the initial TPU content. Preliminary cytotoxicity tests were conducted using NIH 3T3 fibroblast cells. The high survival rate of these cells and the mineralization behavior suggest biocompatibility and high potential of these composites being used in bone tissue engineering applications.


Apatite Simulated Body Fluid Hard Segment Composite Scaffold Liquid Phase Separation 
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, the China Scholarship Council, and the financial support of the National Nature Science Foundation of China (Nos. 51073061, 21174044), the Guangdong Nature Science Foundation (No. S2013020013855), the Fundamental Research Funds for Central Universities (No. 2011ZZ0011), and the 973 Program (2012CB025902) in China.


  1. 1.
    Brighton CT, Shaman P, Heppenstall RB, Esterhai JL, Pollack SR, Friedenberg ZB (1995) Tibial nonunion treated with direct-current, capacitive coupling, or bone-graft. Clin Orthop Relat R 321:223–234Google Scholar
  2. 2.
    Fernyhough JC, Schimandle JJ, Weigel MC, Edwards CC, Levine AM (1992) Chronic donor site pain complicating bone-graft harvesting from the posterior iliac crest for spinal-fusion. Spine 17:1474–1480CrossRefGoogle Scholar
  3. 3.
    Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36:20–27CrossRefGoogle Scholar
  4. 4.
    Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926CrossRefGoogle Scholar
  5. 5.
    Mikos AG, Thorsen AJ, Czerwonka LA et al (1994) Preparation and characterization of poly(l-lactic acid) foams. Polymer 35:1068–1077CrossRefGoogle Scholar
  6. 6.
    Nakamatsu J, Torres FG, Troncoso OP, Yuan ML, Boccaccini AR (2006) Processing and characterization of porous structures from chitosan and starch for tissue engineering scaffolds. Biomacromolecules 7:3345–3355CrossRefGoogle Scholar
  7. 7.
    Wang L, Shi J, Liu L, Secret E, Chen Y (2011) Fabrication of polymer fiber scaffolds by centrifugal spinning for cell culture studies. Microelectron Eng 88:1718–1721CrossRefGoogle Scholar
  8. 8.
    Park SA, Kim HJ, Lee SH et al (2011) Fabrication of nano/microfiber scaffolds using a combination of rapid prototyping and electrospinning systems. Polym Eng Sci 51:1883–1890CrossRefGoogle Scholar
  9. 9.
    Corre YM, Maazouz A, Duchet J, Reignier J (2011) Batch foaming of chain extended PLA with supercritical CO2: influence of the rheological properties and the process parameters on the cellular structure. J Supercrit Fluid 58:177–188CrossRefGoogle Scholar
  10. 10.
    Kramschuster A, Turng LS (2010) An Injection molding process for manufacturing highly porous and interconnected biodegradable polymer matrices for use as tissue engineering scaffolds. J Biomed Mater Res B 92B:366–376Google Scholar
  11. 11.
    Rowlands AS, Lim SA, Martin D, Cooper-White JJ (2007) Polyurethane/poly(lactic-co-glycolic) acid composite scaffolds fabricated by thermally induced phase separation. Biomaterials 28:2109–2121CrossRefGoogle Scholar
  12. 12.
    He LM, Zhang YQ, Zeng X et al (2009) Fabrication and characterization of poly(l-lactic acid) 3D nanofibrous scaffolds with controlled architecture by liquid–liquid phase separation from a ternary polymer-solvent system. Polymer 50:4128–4138CrossRefGoogle Scholar
  13. 13.
    Lo H, Ponticiello MS, Leong KW (1995) Fabrication of controlled release biodegradable foams by phase separation. Tissue Eng 1:15–28CrossRefGoogle Scholar
  14. 14.
    Geiger M, Li RH, Friess W (2003) Collagen sponges for bone regeneration with rhBMP-2. Adv Drug Deliver Rev 55:1613–1629CrossRefGoogle Scholar
  15. 15.
    Li C, Wang LL, Yang Z, Kim G, Chen HF, Ge ZG (2012) A viscoelastic chitosan-modified three-dimensional porous poly(l-Lactide-co-epsilon-caprolactone) scaffold for cartilage tissue engineering. J Biomat Sci-Polym E 23:405–424CrossRefGoogle Scholar
  16. 16.
    Montjovent MO, Mark S, Mathieu L et al (2008) Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering. Bone 42:554–564CrossRefGoogle Scholar
  17. 17.
    Mondrinos MJ, Dembzynski R, Lu L et al (2006) Porogen-based solid freeform fabrication of polycaprolactone-calcium phosphate scaffolds for tissue engineering. Biomaterials 27:4399–4408CrossRefGoogle Scholar
  18. 18.
    Lian C, Wei L, Yilin C (2012) Modification of fibrous PLGA scaffold or PLGA micro-particles with tripolyphosphate nanoparticles. J Tissue Eng Regen M 6:214CrossRefGoogle Scholar
  19. 19.
    Buschmann J, Harter L, Gao SP et al (2012) Tissue engineered bone grafts based on biomimetic nanocomposite PLGA/amorphous calcium phosphate scaffold and human adipose-derived stem cells. Injury 43:1689–1697CrossRefGoogle Scholar
  20. 20.
    Hofmann A, Ritz U, Verrier S et al (2008) The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds. Biomaterials 29:4217–4226CrossRefGoogle Scholar
  21. 21.
    McClure MJ, Wolfe PS, Rodriguez IA, Bowlin GL (2011) Bioengineered vascular grafts: improving vascular tissue engineering through scaffold design. J Drug Deliv Sci Tec 21:211–227Google Scholar
  22. 22.
    Amoroso NJ, D’Amore A, Hong Y, Rivera CP, Sacks MS, Wagner WR (2012) Microstructural manipulation of electrospun scaffolds for specific bending stiffness for heart valve tissue engineering. Acta Biomater 8:4268–4277CrossRefGoogle Scholar
  23. 23.
    Hausner T, Schmidhammer R, Zandieh S et al (2007) Nerve regeneration using tubular scaffolds from biodegradable polyurethane. Acta Neurochir Suppl 100:69–72CrossRefGoogle Scholar
  24. 24.
    Heo DN, Yang DH, Lee JB et al (2013) Burn-wound healing effect of gelatin/polyurethane nanofiber scaffold containing silver-sulfadiazine. J Biomed Nanotechnol 9:511–515CrossRefGoogle Scholar
  25. 25.
    Yoshii T, Hafeman AE, Nyman JS et al (2010) A sustained release of lovastatin from biodegradable elastomeric polyurethane scaffolds for enhanced bone regeneration. Tissue Eng Part A 16:2369–2379CrossRefGoogle Scholar
  26. 26.
    Jack KS, Velayudhan S, Luckman P, Trau M, Grondahl L, Cooper-White J (2009) The fabrication and characterization of biodegradable HA/PHBV nanoparticle-polymer composite scaffolds. Acta Biomater 5:2657–2667CrossRefGoogle Scholar
  27. 27.
    Duan B, Wang M (2010) Customized Ca-P/PHBV nanocomposite scaffolds for bone tissue engineering: design, fabrication, surface modification and sustained release of growth factor. J R Soc Interface 7:S615–S629CrossRefGoogle Scholar
  28. 28.
    Boccaccini AR, Maquet V (2003) Bioresorbable and bioactive polymer/bioglass (R) composites with tailored pore structure for tissue engineering applications. Compos Sci Technol 63:2417–2429CrossRefGoogle Scholar
  29. 29.
    Habibovic P, Gbureck U, Doillon CJ, Bassett DC, van Blitterswijk CA, Barralet JE (2008) Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants. Biomaterials 29:944–953CrossRefGoogle Scholar
  30. 30.
    Stevens MM, George JH (2005) Exploring and engineering the cell surface interface. Science 310:1135–1138CrossRefGoogle Scholar
  31. 31.
    Andric T, Wright LD, Taylor BL, Freeman JW (2012) Fabrication and characterization of three-dimensional electrospun scaffolds for bone tissue engineering. J Biomed Mater Res A 100A:2097–2105CrossRefGoogle Scholar
  32. 32.
    Venugopal JR, Low S, Choon AT, Kumar AB, Ramakrishna S (2008) Nanobioengineered electrospun composite nanofibers and osteoblasts for bone regeneration. Artif Organs 32:388–397CrossRefGoogle Scholar
  33. 33.
    Yang DZ, Jin Y, Ma GP, Chen XM, Lu FM, Nie J (2008) Fabrication and characterization of chitosan/PVA with hydroxyapatite biocomposite nanoscaffolds. J Appl Polym Sci 110:3328–3335CrossRefGoogle Scholar
  34. 34.
    Sheikh FA, Kanjwal MA, Macossay J, Barakat NAM, Kim HY (2012) A simple approach for synthesis, characterization and bioactivity of bovine bones to fabricate the polyurethane nanofiber containing hydroxyapatite nanoparticle. Express Polym Lett 6:41–53CrossRefGoogle Scholar
  35. 35.
    Wang L, Zuo Y, Zou Q, Li YB (2011) Effect of composition on physical-chemical properties and biological properties of hydroxyapatite/aliphatic polyurethane scaffolds for bone tissue engineering. Chem J Chinese Univ 32:2453–2459Google Scholar
  36. 36.
    Kokubo T (1991) Bioactive glass-ceramics—properties and applications. Biomaterials 12:155–163CrossRefGoogle Scholar
  37. 37.
    Kokubo T, Ito S, Huang ZT et al (1990) Ca, P-rich layer formed on high-strength bioactive glass-ceramic a-W. J Biomed Mater Res 24:331–343CrossRefGoogle Scholar
  38. 38.
    Ohtsuki C, Kushitani H, Kokubo T, Kotani S, Yamamuro T (1991) Apatite formation on the surface of ceravital-type glass-ceramic in the body. J Biomed Mater Res 25:1363–1370CrossRefGoogle Scholar
  39. 39.
    Legeros RZ, Lin S, Rohanizadeh R, Mijares D, Legeros JP (2003) Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Mater Sci-Mater M 14:201–209CrossRefGoogle Scholar
  40. 40.
    Li PJ, Ohtsuki C, Kokubo T, Nakanishi K, Soga N, Degroot K (1994) The role of hydrated silica, titania, and alumina in inducing apatite on implants. J Biomed Mater Res 28:7–15CrossRefGoogle Scholar
  41. 41.
    Deplaine H, Lebourg M, Ripalda P et al (2013) Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(l-lactic acid) scaffolds. J Biomed Mater Res B 101B:173–186CrossRefGoogle Scholar
  42. 42.
    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
  43. 43.
    Kokubo T, Takadama H (2006) How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27:2907–2915CrossRefGoogle Scholar
  44. 44.
    Panda RN, Hsieh MF, Chung RJ, Chin TS (2003) FTIR, XRD, SEM and solid state NMR investigations of carbonate-containing hydroxyapatite nano-particles synthesized by hydroxide-gel technique. J Phys Chem Solids 64:193–199CrossRefGoogle Scholar
  45. 45.
    Mobasherpour I, Heshajin MS, Kazemzadeh A, Zakeri M (2007) Synthesis of nanocrystalline hydroxyapatite by using precipitation method. J Alloy Compd 430:330–333CrossRefGoogle Scholar
  46. 46.
    Schugens C, Maquet V, Grandfils C, Jerome R, Teyssie P (1996) Biodegradable and macroporous polylactide implants for cell transplantation. 1. Preparation of macroporous polylactide supports by solid–liquid phase separation. Polymer 37:1027–1038CrossRefGoogle Scholar
  47. 47.
    Wang XH, Shi SA, Guo G et al (2011) Preparation and characterization of a porous scaffold based on poly(d, l-lactide) and N-hydroxyapatite by phase separation. J Biomat Sci-Polym E 22:1917–1929CrossRefGoogle Scholar
  48. 48.
    Hench LL, Wilson J (1993) An introduction to bioceramics. World Scientific, London and SingaporeCrossRefGoogle Scholar
  49. 49.
    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
  50. 50.
    Lluch AV, Ferrer GG, Pradas MM (2009) Surface modification of P(EMA-co-HEA)/SiO2 nanohybrids for faster hydroxyapatite deposition in simulated body fluid? Colloid Surface B 70:218–225CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Hao-Yang Mi
    • 1
    • 2
    • 5
  • Xin Jing
    • 1
    • 2
    • 5
  • Max R. Salick
    • 3
  • Travis M. Cordie
    • 4
  • Xiang-Fang Peng
    • 2
  • Lih-Sheng Turng
    • 1
    • 5
  1. 1.Wisconsin Institutes for DiscoveryUniversity of Wisconsin–MadisonMadisonUSA
  2. 2.National Engineering Research Center of Novel Equipment for Polymer ProcessingSouth China University of TechnologyGuangzhouChina
  3. 3.Department of Engineering PhysicsUniversity of Wisconsin–MadisonMadisonUSA
  4. 4.Department of Biomedical EngineeringUniversity of Wisconsin–MadisonMadisonUSA
  5. 5.Department of Mechanical EngineeringUniversity of Wisconsin–MadisonMadisonUSA

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