Comparative Assessment of the Ability of Dual-Pore Structure and Hydroxyapatite to Enhance the Proliferation of Osteoblast-Like Cells in Well-Interconnected Scaffolds

  • Yong Sang Cho
  • Joon Sup Lee
  • Myoung Wha Hong
  • Se-Hwan Lee
  • Young Yul Kim
  • Young-Sam Cho
Regular Paper


In this study, to compare the relative abilities of dual-pore structure and hydroxyapatite to enhance the proliferation of osteoblastlike cell in well-interconnected scaffolds, several types of scaffolds were fabricated using combined SLUP (Salt-Leaching Using Powder) and WNM (Wire-Network Molding) techniques: well-interconnected dual-pore scaffolds with hydroxyapatite particles, wellinterconnected dual-pore scaffolds without hydroxyapatite particles, and single-pore scaffolds with hydroxyapatite particles. To assess the characteristics of the fabricated scaffolds, their morphology, compressive modulus, water absorption, and in-vitro cell activity were measured. Consequently, it was found that while the hydroxyapatite (which is hydrophilic) provides some advantage for cell attachment, the cell attachment in the dual-pore scaffold with hydroxyapatite particles was similar to that of the dual-pore scaffold without hydroxyapatite particles. Moreover, regarding cell proliferation, we verified that the effect of the dual-pore structure was dominant compared with the existence of hydroxyapatite particles and co-existence of dual-pore structure/hydroxyapatite particles. However, the cell vitality of the dual-pore scaffold with hydroxyapatite particles was higher than that of the dual-pore scaffold without hydroxyapatite particles because of ions released by the hydroxyapatite particles.


Tissue engineering Dual-pore structure Hydroxyapatite Wire-network molding Salt-leaching using powder 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Akbarzadeh, R., Minton, J. A., Janney, C. S., Smith, T. A., James, P. F., and Yousefi, A.-M., “Hierarchical Polymeric Scaffolds Support the Growth of MC3T3-E1 Cells,” Journal of Materials Science: Materials in Medicine, Vol. 26, No. 2, Paper No. 116, 2015.Google Scholar
  2. 2.
    Cancedda, R., Dozin, B., Giannoni, P., and Quarto, R., “Tissue Engineering and Cell Therapy of Cartilage and Bone,” Matrix Biology, Vol. 22, No. 1, pp. 81–91, 2003.CrossRefGoogle Scholar
  3. 3.
    Hollister, S. J., Maddox, R. D., and Taboas, J. M., “Optimal Design and Fabrication of Scaffolds to Mimic Tissue Properties and Satisfy Biological Constraints,” Biomaterials, Vol. 23, No. 20, pp. 4095–4103, 2002.CrossRefGoogle Scholar
  4. 4.
    Wei, C. and Dong, J., “Hybrid Hierarchical Fabrication of Three-Dimensional Scaffolds,” Journal of Manufacturing Processes, Vol. 16, No. 2, pp. 257–263, 2014.CrossRefGoogle Scholar
  5. 5.
    Seyednejad, H., Gawlitta, D., Kuiper, R. V., de Bruin, A., van Nostrum, C. F., et al., “In Vivo Biocompatibility and Biodegradation of 3D-Printed Porous Scaffolds Based on a Hydroxyl-Functionalized Poly (e-Caprolactone),” Biomaterials, Vol. 33, No. 17, pp. 4309–4318, 2012.CrossRefGoogle Scholar
  6. 6.
    Heo, S. J., Kim, S. E., Wei, J., Hyun, Y. T., Yun, H. S., et al., “Fabrication and Characterization of Novel Nano-and Micro-HA/ PCL Composite Scaffolds Using a Modified Rapid Prototyping Process,” Journal of Biomedical Materials Research Part A, Vol. 89, No. 1, pp. 108–116, 2009.Google Scholar
  7. 7.
    Ding, X., Wei, X., Huang, Y., Guan, C., Zou, T., et al., “Delivery of Demineralized Bone Matrix Powder Using a Salt-Leached Silk Fibroin Carrier for Bone Regeneration,” Journal of Materials Chemistry B, Vol. 3, No. 16, pp. 3177–3188, 2015.CrossRefGoogle Scholar
  8. 8.
    Thein-Han, W. W., and Xu, H. H. K., “Prevascularization of a Gas-Foaming Macroporous Calcium Phosphate Cement Scaffold via Coculture of Human Umbilical Vein Endothelial Cells and Osteoblasts,” Tissue Engineering Part A, Vol. 19, No. 15-16, pp. 1675–1685, 2013.CrossRefGoogle Scholar
  9. 9.
    Taherkhani, S. and Moztarzadeh, F., “Fabrication of a Poly (e-Caprolactone)/Starch Nanocomposite Scaffold with a Solvent-Casting/Salt-Leaching Technique for Bone Tissue Engineering Applications,” Journal of Applied Polymer Science, Vol. 133, No. 23, Paper No. 43523, 2016.Google Scholar
  10. 10.
    Yu, N. Y., Schindeler, A., Peacock, L., Mikulec, K., Fitzpatrick, J., et al., “Modulation of Anabolic and Catabolic Responses via a Porous Polymer Scaffold Manufactured Using Thermally Induced Phase Separation,” European Cells and Materials, Vol. 25, pp. 190–203, 2013.CrossRefGoogle Scholar
  11. 11.
    Nie, L., Chen, D., Suo, J., Zou, P., Feng, S., et al., “Physicochemical Characterization and Biocompatibility in Vitro of Biphasic Calcium Phosphate/Polyvinyl Alcohol Scaffolds Prepared by Freeze-Drying Method for Bone Tissue Engineering Applications,” Colloids and Surfaces B: Biointerfaces, Vol. 100, pp. 169–176, 2012.CrossRefGoogle Scholar
  12. 12.
    Weng, L., Teusink, M. J., Shuler, F. D., Parecki, V., and Xie, J., “Highly Controlled Coating of Strontium-Doped Hydroxyapatite on Electrospun Poly (e-Caprolactone) Fibers,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 105, No. 4, pp. 753–763, 2017.CrossRefGoogle Scholar
  13. 13.
    Ronca, A., Ambrosio, L., and Grijpma, D. W., “Preparation of Designed Poly (D, L-Lactide)/Nanosized Hydroxyapatite Composite Structures by Stereolithography,” Acta biomaterialia, Vol. 9, No. 4, pp. 5989–5996, 2013.CrossRefGoogle Scholar
  14. 14.
    Shuai, C., Gao, C., Nie, Y., Hu, H., Zhou, Y., and Peng, S., “Structure and Properties of Nano-Hydroxypatite Scaffolds for Bone Tissue Engineering with a Selective Laser Sintering System,” Nanotechnology, Vol. 22, No. 28, Paper No. 285703, 2011.Google Scholar
  15. 15.
    Luo, Y., Lode, A., Wu, C., Chang, J., and Gelinsky, M., “Alginate/ Nanohydroxyapatite Scaffolds with Designed Core/Shell Structures Fabricated by 3D Plotting and in situ Mineralization for Bone Tissue Engineering,” ACS Applied Materials & Interfaces, Vol. 7, No. 12, pp. 6541–6549, 2015.CrossRefGoogle Scholar
  16. 16.
    Kang, H.-W., Rhie, J.-W., and Cho, D.-W., “Development of a Bi-Pore Scaffold Using Indirect Solid Freeform Fabrication Based on Microstereolithography Technology,” Microelectronic Engineering, Vol. 86, Nos. 4-6, pp. 941–944, 2009.CrossRefGoogle Scholar
  17. 17.
    Park, K., Jung, H. J., Son, J. S., Park, K. D., Kim, J. J., et al., “Preparation of Biodegradable Polymer Scaffolds with Dual Pore System for Tissue Regeneration,” Macromolecular Symposia, Vols. 249-250, No. 1, pp. 145–150, 2007.CrossRefGoogle Scholar
  18. 18.
    Mohanty, S., Sanger, K., Heiskanen, A., Trifol, J., Szabo, P., et al., “Fabrication of Scalable Tissue Engineering Scaffolds with Dual-Pore Microarchitecture by Combining 3D Printing and particle Leaching,” Materials Science and Engineering: C, Vol. 61, pp. 180–189, 2016.CrossRefGoogle Scholar
  19. 19.
    Park, S. H., Kim, T. G., Kim, H. C., Yang, D.-Y., and Park, T. G., “Development of Dual Scale Scaffolds Via Direct Polymer Melt Deposition and Electrospinning for Applications in Tissue Regeneration,” Acta Biomaterialia, Vol. 4, No. 5, pp. 1198–1207, 2008.CrossRefGoogle Scholar
  20. 20.
    Rizzi, S. C., Heath, D., Coombes, A., Bock, N., Textor, M., and Downes, S., “Biodegradable Polymer/Hydroxyapatite Composites: Surface Analysis and Initial Attachment of Human Osteoblasts,” Journal of Biomedical Materials Research Part A, Vol. 55, No. 4, pp. 475–486, 2001.CrossRefGoogle Scholar
  21. 21.
    Thuaksuban, N., Luntheng, T., and Monmaturapoj, N., “Physical Characteristics and Biocompatibility of the Polycaprolactone-Biphasic Calcium Phosphate Scaffolds Fabricated Using the Modified Melt Stretching and Multilayer Deposition,” Journal of Biomaterials Applications, Vol. 30, No. 10, pp. 1460–1472, 2016.CrossRefGoogle Scholar
  22. 22.
    Seol, Y.-J., Park, J. Y., Jung, J. W., Jang, J., Girdhari, R., et al., “Improvement of Bone Regeneration Capability of Ceramic Scaffolds by Accelerated Release of their Calcium Ions,” Tissue Engineering Part A, Vol. 20, Nos. 21-22, pp. 2840–2849, 2014.CrossRefGoogle Scholar
  23. 23.
    Cho, Y. S., Hong, M. W., Kim, S.-Y., Lee, S.-J., Lee, J. H., et al., “Fabrication of Dual-Pore Scaffolds Using SLUP (Salt Leaching Using Powder) and WNM (Wire-Network Molding) Techniques,” Materials Science and Engineering: C, Vol. 45, pp. 546–555, 2014.CrossRefGoogle Scholar
  24. 24.
    Cho, Y. S., Hong, M. W., Jeong, H. J., Lee, S. J., Kim, Y. Y., and Cho, Y. S., “The Fabrication of Well-Interconnected Polycaprolactone/ Hydroxyapatite Composite Scaffolds, Enhancing the Exposure of Hydroxyapatite Using the Wire-Network Molding Technique,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 105, No. 8, pp. 2315–2325, 2017.CrossRefGoogle Scholar
  25. 25.
    Chen, G., Zhou, P., Mei, N., Chen, X., Shao, Z., et al., “Silk Fibroin Modified Porous Poly (e-Caprolactone) Scaffold for Human Fibroblast Culture in Vitro,” Journal of Materials Science: Materials in Medicine, Vol. 15, No. 6, pp. 671–677, 2004.CrossRefGoogle Scholar
  26. 26.
    Li, X., Shi, J., Dong, X., Zhang, L., and Zeng, H., “A Mesoporous Bioactive Glass/Polycaprolactone Composite Scaffold and Its Bioactivity Behavior,” Journal of Biomedical Materials Research Part A, Vol. 84, No. 1, pp. 84–91, 2008.Google Scholar
  27. 27.
    Oh, S. H., Kang, S. G., Kim, E. S., Cho, S. H., and Lee, J. H., “Fabrication and Characterization of Hydrophilic Poly (Lactic-Co-Glycolic Acid)/Poly (Vinyl Alcohol) Blend Cell Scaffolds by Melt-Molding Particulate-Leaching Method,” Biomaterials, Vol. 24, No. 22, pp. 4011–4021, 2003.CrossRefGoogle Scholar
  28. 28.
    Oh, S. H., Kang, S. G., and Lee, J. H., “Degradation Behavior of Hydrophilized PLGA Scaffolds Prepared by Melt-Molding Particulate-Leaching Method: Comparison with Control Hydrophobic One,” Journal of Materials Science: Materials in Medicine, Vol. 17, No. 2, pp. 131–137, 2006.Google Scholar
  29. 29.
    Makaya, K., Terada, S., Ohgo, K., and Asakura, T., “Comparative Study of Silk Fibroin Porous Scaffolds Derived from Salt/Water and Sucrose/Hexafluoroisopropanol in Cartilage Formation,” Journal of Bioscience and Bioengineering, Vol. 108, No. 1, pp. 68–75, 2009.CrossRefGoogle Scholar
  30. 30.
    Oh, S. H., Park, S. C., Kim, H. K., Koh, Y. J., Lee, J.-H., et al., “Degradation Behavior of 3D Porous Polydioxanone-b-Polycaprolactone Scaffolds Fabricated Using the Melt-Molding Particulate-Leaching Method,” Journal of Biomaterials Science, Polymer Edition, Vol. 22, Nos. 1-3, pp. 225–237, 2011.CrossRefGoogle Scholar
  31. 31.
    Gere, J. M., “Mechanics of Materials,” Thomson, 6th Ed. 2004.Google Scholar
  32. 32.
    Hong, S. and Kim, G., “Fabrication of Electrospun Polycaprolactone Biocomposites Reinforced with Chitosan for the Proliferation of Mesenchymal Stem Cells,” Carbohydrate Polymers, Vol. 83, No. 2, pp. 940–946, 2011.CrossRefGoogle Scholar
  33. 33.
    Lee, H., Yeo, M., Ahn, S., Kang, D. O., Jang, C. H., et al., “Designed Hybrid Scaffolds Consisting of Polycaprolactone Microstrands and Electrospun Collagen-Nanofibers for Bone Tissue Regeneration,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 97, No. 2, pp. 263–270, 2011.CrossRefGoogle Scholar
  34. 34.
    Shen, H., Hu, X., Yang, F., Bei, J., and Wang, S., “An Injectable Scaffold: RhBMP-2-Loaded Poly (Lactide-Co-Glycolide)/ Hydroxyapatite Composite Microspheres,” Acta Biomaterialia, Vol. 6, No. 2, pp. 455–465, 2010.CrossRefGoogle Scholar

Copyright information

© Korean Society for Precision Engineering and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Mechanical and Automotive Engineering, College of EngineeringWonkwang UniversityJeollabuk-doRepublic of Korea
  2. 2.Department of Mechanical Design Engineering, College of EngineeringWonkwang UniversityJeollabuk-doRepublic of Korea
  3. 3.Department of Orthopedics, Daejeon St. Mary’s HospitalCatholic University of KoreaDaejeonRepublic of Korea

Personalised recommendations