Experimental and computational characterization of designed and fabricated 50:50 PLGA porous scaffolds for human trabecular bone applications

  • Eiji Saito
  • Heesuk Kang
  • Juan M. Taboas
  • Alisha Diggs
  • Colleen L. Flanagan
  • Scott J. Hollister


The present study utilizes image-based computational methods and indirect solid freeform fabrication (SFF) technique to design and fabricate porous scaffolds, and then computationally estimates their elastic modulus and yield stress with experimental validation. 50:50 Poly (lactide-co-glycolide acid) (50:50 PLGA) porous scaffolds were designed using an image-based design technique, fabricated using indirect SFF technique, and characterized using micro-computed tomography (μ-CT) and mechanical testing. μ-CT data was further used to non-destructively predict the scaffold elastic moduli and yield stress using a voxel-based finite element (FE) method, a technique that could find application in eventual scaffold quality control. μ-CT data analysis confirmed that the fabricated scaffolds had controlled pore sizes, orthogonally interconnected pores and porosities which were identical to those of the designed files. Mechanical tests revealed that the compressive modulus and yield stresses were in the range of human trabecular bone. The results of FE analysis showed potential stress concentrations inside of the fabricated scaffold due to fabrication defects. Furthermore, the predicted moduli and yield stresses of the FE analysis showed strong correlations with those of the experiments. In the present study, we successfully fabricated scaffolds with designed architectures as well as predicted their mechanical properties in a nondestructive manner.


Poly Lactic Acid Compressive Modulus Porous Scaffold Solid Freeform Fabrication Interactive Data Language 
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.



This study was supported by National Institute of Health (NIH) R01 grant AR 053379. We also would like to thank for Prof. John Halloran in Materials Science and Engineering for letting us to use their tube furnace and sintering oven.


  1. 1.
    Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26:5474–91.CrossRefPubMedGoogle Scholar
  2. 2.
    Athanasiou KA, Agrawal CM, Barber FA, Burkhart SS. Orthopaedic applications for PLA-PGA biodegradable polymers. Arthroscopy. 1998;14:726–37.CrossRefPubMedGoogle Scholar
  3. 3.
    Hutmacher DW. Scaffold design and fabrication technologies for engineering tissues–state of the art and future perspectives. J Biomater Sci Polym Ed. 2001;12:107–24.CrossRefPubMedGoogle Scholar
  4. 4.
    Hollister SJ. Porous scaffold design for tissue engineering. Nat Mater. 2005;4:518–24.CrossRefPubMedADSGoogle Scholar
  5. 5.
    Ma PX, Choi JW. Biodegradable polymer scaffolds with well-defined interconnected spherical pore network. Tissue Eng. 2001;7:23–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Murphy WL, Dennis RG, Kileny JL, Mooney DJ. Salt fusion: an approach to improve pore interconnectivity within tissue engineering scaffolds. Tissue Eng. 2002;8:43–52.CrossRefPubMedGoogle Scholar
  7. 7.
    Guan L, Davies JE. Preparation and characterization of a highly macroporous biodegradable composite tissue engineering scaffold. J Biomed Mater Res A. 2004;71:480–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Huang YX, Ren J, Chen C, Ren TB, Zhou XY. Preparation and properties of poly(lactide-co-glycolide) (PLGA)/nano-hydroxyapatite (NHA) scaffolds by thermally induced phase separation and rabbit MSCs culture on scaffolds. J Biomater Appl. 2008;22:409–32.CrossRefPubMedGoogle Scholar
  9. 9.
    Hu Y, Grainger DW, Winn SR, Hollinger JO. Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems. J Biomed Mater Res. 2002;59:563–72.CrossRefPubMedGoogle Scholar
  10. 10.
    Nam YS, Park TG. Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. J Biomed Mater Res. 1999;47:8–17.CrossRefPubMedGoogle Scholar
  11. 11.
    Thomson RC, Yaszemski MJ, Powers JM, Mikos AG. Fabrication of biodegradable polymer scaffolds to engineer trabecular bone. J Biomater Sci Polym Ed. 1995;7:23–38.CrossRefPubMedGoogle Scholar
  12. 12.
    Wu L, Zhang H, Zhang J, Ding J. Fabrication of three-dimensional porous scaffolds of complicated shape for tissue engineering. I. Compression molding based on flexible-rigid combined mold. Tissue Eng. 2005;11:1105–14.CrossRefPubMedGoogle Scholar
  13. 13.
    Harris LD, Kim BS, Mooney DJ. Open pore biodegradable matrices formed with gas foaming. J Biomed Mater Res. 1998;42:396–402.CrossRefPubMedGoogle Scholar
  14. 14.
    Thomson RC, Yaszemski MJ, Powers JM, Mikos AG. Hydroxyapatite fiber reinforced poly(alpha-hydroxy ester) foams for bone regeneration. Biomaterials. 1998;19:1935–43.CrossRefPubMedGoogle Scholar
  15. 15.
    Lu HH, El-Amin SF, Scott KD, Laurencin CT. Three-dimensional, bioactive, biodegradable, polymer-bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro. J Biomed Mater Res A. 2003;64:465–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials. 2006;27:3413–31.CrossRefPubMedGoogle Scholar
  17. 17.
    Karande TS, Ong JL, Agrawal CM. Diffusion in musculoskeletal tissue engineering scaffolds: design issues related to porosity, permeability, architecture, and nutrient mixing. Ann Biomed Eng. 2004;32:1728–43.CrossRefPubMedGoogle Scholar
  18. 18.
    Lee KW, Wang S, Fox BC, Ritman EL, Yaszemski MJ, Lu L. Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. Biomacromolecules. 2007;8:1077–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Hollister SJ, Lin CY, Saito E, Lin CY, Schek RD, Taboas JM, Williams JM, Partee B, Flanagan CL, Diggs A, Wilke EN, Van Lenthe GH, Muller R, Wirtz T, Das S, Feinberg SE, Krebsbach PH. Engineering craniofacial scaffolds. Orthod Craniofac Res. 2005;8:162–73.CrossRefPubMedGoogle Scholar
  20. 20.
    Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH, Feinberg SE, Hollister SJ, Das S. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials. 2005;26:4817–27.CrossRefPubMedGoogle Scholar
  21. 21.
    Hutmacher DW, Schantz T, Zein I, Ng KW, Teoh SH, Tan KC. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J Biomed Mater Res. 2001;55:203–16.CrossRefPubMedGoogle Scholar
  22. 22.
    Hsu SH, Yen HJ, Tseng CS, Cheng CS, Tsai CL. Evaluation of the growth of chondrocytes and osteoblasts seeded into precision scaffolds fabricated by fused deposition manufacturing. J Biomed Mater Res B Appl Biomater. 2007;80:519–27.PubMedGoogle Scholar
  23. 23.
    Sherwood JK, Riley SL, Palazzolo R, Brown SC, Monkhouse DC, Coates M, Griffith LG, Landeen LK, Ratcliffe A. A three-dimensional osteochondral composite scaffold for articular cartilage repair. Biomaterials. 2002;23:4739–51.CrossRefPubMedGoogle Scholar
  24. 24.
    Weigel T, Schinkel G, Lendlein A. Design and preparation of polymeric scaffolds for tissue engineering. Expert Rev Med Devices. 2006;3:835–51.CrossRefPubMedGoogle Scholar
  25. 25.
    Taboas JM, Maddox RD, Krebsbach PH, Hollister SJ. Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer-ceramic scaffolds. Biomaterials. 2003;24:181–94.CrossRefPubMedGoogle Scholar
  26. 26.
    Chen VJ, Smith LA, Ma PX. Bone regeneration on computer-designed nano-fibrous scaffolds. Biomaterials. 2006;27:3973–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Lee KW, Wang S, Lu L, Jabbari E, Currier BL, Yaszemski MJ. Fabrication and characterization of poly(propylene fumarate) scaffolds with controlled pore structures using 3-dimensional printing and injection molding. Tissue Eng. 2006;12:2801–11.CrossRefPubMedGoogle Scholar
  28. 28.
    Liao E, Yaszemski M, Krebsbach P, Hollister S. Tissue-engineered cartilage constructs using composite hyaluronic acid/collagen I hydrogels and designed poly(propylene fumarate) scaffolds. Tissue Eng. 2007;13:537–50.CrossRefPubMedGoogle Scholar
  29. 29.
    Roosa SM, Kemppainen JM, Moffitt EN, Krebsbach PH, Hollister SJ. The pore size of polycaprolactone scaffolds has limited influence on bone regeneration in an in vivo model. J Biomed Mater Res A. 2010;92:359–68.PubMedGoogle Scholar
  30. 30.
    Lin CY, Schek RM, Mistry AS, Shi X, Mikos AG, Krebsbach PH, Hollister SJ. Functional bone engineering using ex vivo gene therapy and topology-optimized, biodegradable polymer composite scaffolds. Tissue Eng. 2005;11:1589–98.CrossRefPubMedGoogle Scholar
  31. 31.
    Howk D, Chu TM. Design variables for mechanical properties of bone tissue scaffolds. Biomed Sci Instrum. 2006;42:278–83.PubMedGoogle Scholar
  32. 32.
    Middleton JC, Tipton AJ. Synthetic biodegradable polymers as orthopedic devices. Biomaterials. 2000;21:2335–46.CrossRefPubMedGoogle Scholar
  33. 33.
    Sosnowski S, Wozniak P, Lewandowska-Szumiel M. Polyester scaffolds with bimodal pore size distribution for tissue engineering. Macromol Biosci. 2006;6:425–34.CrossRefPubMedGoogle Scholar
  34. 34.
    Wu L, Ding J. In vitro degradation of three-dimensional porous poly(d, l-lactide-co-glycolide) scaffolds for tissue engineering. Biomaterials. 2004;25:5821–30.CrossRefPubMedGoogle Scholar
  35. 35.
    Kim SS, Sun Park M, Jeon O, Yong Choi C, Kim BS. Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering. Biomaterials. 2006;27:1399–409.CrossRefPubMedGoogle Scholar
  36. 36.
    Ma PX, Zhang R. Microtubular architecture of biodegradable polymer scaffolds. J Biomed Mater Res. 2001;56:469–77.CrossRefPubMedGoogle Scholar
  37. 37.
    Wu L, Ding J. Effects of porosity and pore size on in vitro degradation of three-dimensional porous poly(d, l-lactide-co-glycolide) scaffolds for tissue engineering. J Biomed Mater Res A. 2005;75:767–77.PubMedGoogle Scholar
  38. 38.
    Jiang T, Abdel-Fattah WI, Laurencin CT. In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering. Biomaterials. 2006;27:4894–903.CrossRefPubMedGoogle Scholar
  39. 39.
    Sun W, Starly B, Darling A, Gomez C. Computer-aided tissue engineering: application to biomimetic modelling and design of tissue scaffolds. Biotechnol Appl Biochem. 2004;39:49–58.CrossRefPubMedGoogle Scholar
  40. 40.
    Hollister SJ, Levy RA, Chu TM, Halloran JW, Feinberg SE. An image-based approach for designing and manufacturing craniofacial scaffolds. Int J Oral Maxillofac Surg. 2000;29:67–71.CrossRefPubMedGoogle Scholar
  41. 41.
    Hollister SJ, Maddox RD, Taboas JM. Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. Biomaterials. 2002;23:4095–103.CrossRefPubMedGoogle Scholar
  42. 42.
    Lin CY, Kikuchi N, Hollister SJ. A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity. J Biomech. 2004;37:623–36.CrossRefPubMedGoogle Scholar
  43. 43.
    Ho ST, Hutmacher DW. A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials. 2006;27:1362–76.CrossRefPubMedGoogle Scholar
  44. 44.
    van Lenthe GH, Hagenmuller H, Bohner M, Hollister SJ, Meinel L, Muller R. Nondestructive micro-computed tomography for biological imaging and quantification of scaffold-bone interaction in vivo. Biomaterials. 2007;28:2479–90.CrossRefPubMedGoogle Scholar
  45. 45.
    Charles-Harris M, del Valle S, Hentges E, Bleuet P, Lacroix D, Planell JA. Mechanical and structural characterisation of completely degradable polylactic acid/calcium phosphate glass scaffolds. Biomaterials. 2007;28:4429–38.CrossRefPubMedGoogle Scholar
  46. 46.
    Lacroix D, Chateau A, Ginebra MP, Planell JA. Micro-finite element models of bone tissue-engineering scaffolds. Biomaterials. 2006;27:5326–34.CrossRefPubMedGoogle Scholar
  47. 47.
    Duty AO, Oest ME, Guldberg RE. Cyclic mechanical compression increases mineralization of cell-seeded polymer scaffolds in vivo. J Biomech Eng. 2007;129:531–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Jaecques SV, Van Oosterwyck H, Muraru L, Van Cleynenbreugel T, De Smet E, Wevers M, Naert I, Vander Sloten J. Individualised, micro CT-based finite element modelling as a tool for biomechanical analysis related to tissue engineering of bone. Biomaterials. 2004;25:1683–96.CrossRefPubMedGoogle Scholar
  49. 49.
    Chu TM, Halloran JW, Hollister SJ, Feinberg SE. Hydroxyapatite implants with designed internal architecture. J Mater Sci Mater Med. 2001;12:471–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Chu TM, Orton DG, Hollister SJ, Feinberg SE, Halloran JW. Mechanical and in vivo performance of hydroxyapatite implants with controlled architectures. Biomaterials. 2002;23:1283–93.CrossRefPubMedGoogle Scholar
  51. 51.
    Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone. 1993;14:595–608.CrossRefPubMedGoogle Scholar
  52. 52.
    Athanasiou KA, Zhu C, Lanctot DR, Agrawal CM, Wang X. Fundamentals of biomechanics in tissue engineering of bone. Tissue Eng. 2000;6:361–81.CrossRefPubMedGoogle Scholar
  53. 53.
    Hutmacher DW, Schantz JT, Lam CX, Tan KC, Lim TC. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. J Tissue Eng Regen Med. 2007;1:245–60.CrossRefPubMedGoogle Scholar
  54. 54.
    Kim JY, Jin GZ, Park IS, Kim JN, Chun SY, Park EK, Kim SY, Yoo J, Kim SH, Rhie JW, Cho DW. Evaluation of SFF-based scaffolds seeded with osteoblasts and HUVECs for use in vivo osteogenesis. Tissue Eng A. (in press).Google Scholar
  55. 55.
    Mathieu LM, Mueller TL, Bourban PE, Pioletti DP, Muller R, Manson JA. Architecture and properties of anisotropic polymer composite scaffolds for bone tissue engineering. Biomaterials. 2006;27:905–16.CrossRefPubMedGoogle Scholar
  56. 56.
    Alberich-Bayarri A, Moratal D, Ivirico JL, Rodriguez Hernandez JC, Valles-Lluch A, Marti-Bonmati L, Estelles JM, Mano JF, Pradas MM, Ribelles JL, Salmeron-Sanchez M. Microcomputed tomography and microfinite element modeling for evaluating polymer scaffolds architecture and their mechanical properties. J Biomed Mater Res B Appl Biomater. 2009;91:191–202.PubMedGoogle Scholar
  57. 57.
    Diego RB, Estelles JM, Sanz JA, Garcia-Aznar JM, Sanchez MS. Polymer scaffolds with interconnected spherical pores and controlled architecture for tissue engineering: fabrication, mechanical properties, and finite element modeling. J Biomed Mater Res B Appl Biomater. 2007;81:448–55.PubMedGoogle Scholar
  58. 58.
    Miranda P, Pajares A, Guiberteau F. Finite element modeling as a tool for predicting the fracture behavior of robocast scaffolds. Acta Biomater. 2008;4:1715–24.CrossRefPubMedGoogle Scholar
  59. 59.
    Lengsfeld M, Schmitt J, Alter P, Kaminsky J, Leppek R. Comparison of geometry-based and CT voxel-based finite element modelling and experimental validation. Med Eng Phys. 1998;20:515–22.CrossRefPubMedGoogle Scholar
  60. 60.
    Hollister SJ, Brennan JM, Kikuchi N. A homogenization sampling procedure for calculating trabecular bone effective stiffness and tissue level stress. J Biomech. 1994;27:433–44.CrossRefPubMedGoogle Scholar
  61. 61.
    Guldberg RE, Hollister SJ, Charras GT. The accuracy of digital image-based finite element models. J Biomech Eng. 1998;120:289–95.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Eiji Saito
    • 1
  • Heesuk Kang
    • 2
  • Juan M. Taboas
    • 4
  • Alisha Diggs
    • 1
  • Colleen L. Flanagan
    • 1
  • Scott J. Hollister
    • 1
    • 2
    • 3
  1. 1.Department of Biomedical EngineeringUniversity of MichiganAnn ArborUSA
  2. 2.Department of Mechanical EngineeringUniversity of MichiganAnn ArborUSA
  3. 3.Department of SurgeryUniversity of MichiganAnn ArborUSA
  4. 4.Department of Orthopedics SurgeryUniversity of PittsburghPittsburghUSA

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