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In vivo lamellar bone formation in fibre coated MgCHA–PCL-composite scaffolds

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Abstract

Bio-inspired materials with controlled topography have gained increasing interest in regenerative medicine, because of their ability to reproduce the physical features of natural extracellular matrix, thus amplifying certain biological responses both in vitro and in vivo, such as contact guidance and differentiation. However, information on the ability to adapt this high cell potential to 3D scaffolds, effective to be implanted in clinical bone defect, is still missing. Here, we examine the pattern of bone tissue generated within the implant in an ectopic model, seeding bone marrow progenitor cells onto PCL–MgCHA scaffolds. This composite material presented a porous structure with micro/nanostructured surfaces obtained by combining phase inversion/salt leaching and electrospinning techniques. Histological analysis of grafts harvested after 1–2–6 months from implantation highlights an extent of lamellar bone tissue within interconnected pores of fibre coated PCL–MgCHA composites, whereas uncoated scaffolds displayed sparse deposition of bone. Pure PCL scaffolds did not reveal any trace of bone for the overall 6 months of observation. In conclusion, we show that a structural modification in scaffold design is able to enhance bone regeneration possibly mimicking some physiological cues of the natural tissue.

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References

  1. Barrilleaux B, Phinney DG, Prockop DJ, O’Connor KC. Review: ex vivo engineering of living tissues with adult stem cells. Tissue Eng. 2006;12(11):3007–19.

    Article  CAS  Google Scholar 

  2. Cancedda R, Bianchi G, Derubeis A, Quarto R. Cell therapy for bone disease: a review of current status. Stem Cells. 2003;21(5):610–9.

    Article  CAS  Google Scholar 

  3. Logeart-Avramoglou D, Anagnostou F, Bizios R, Petite H. Engineering bone: challenges and obstacles. J Cell Mol Med. 2005;9(1):72–84.

    Article  CAS  Google Scholar 

  4. Oreffo RO, Triffitt JT. Future potentials for using osteogenic stem cells and biomaterials in orthopedics. Bone. 1999;25(2 Suppl):5S–9S.

    Article  CAS  Google Scholar 

  5. Srouji S, Kizhner T, Livne E. 3D scaffolds for bone marrow stem cell support in bone repair. Regen Med. 2006;1(4):519–28.

    Article  CAS  Google Scholar 

  6. Warren SM, Nacamuli RK, Song HM, Longaker MT. Tissue-engineered bone using mesenchymal stem cells and a biodegradable scaffold. J Craniofac Surg. 2004;15(1):34–7.

    Article  Google Scholar 

  7. Cheng L, Ye F, Yang R, Lu X, Shi Y, Li L, et al. Osteoinduction of hydroxyapatite/beta-tricalcium phosphate bioceramics in mice with a fractured fibula. Acta Biomater. 2010;6(4):1569–74.

    Article  CAS  Google Scholar 

  8. Fan H, Ikoma T, Tanaka J, Zhang X. Surface structural biomimetics and the osteoinduction of calcium phosphate biomaterials. J Nanosci Nanotechnol. 2007;7(3):808–13.

    Article  CAS  Google Scholar 

  9. Kondo N, Ogose A, Tokunaga K, Umezu H, Arai K, Kudo N, et al. Osteoinduction with highly purified beta-tricalcium phosphate in dog dorsal muscles and the proliferation of osteoclasts before heterotopic bone formation. Biomaterials. 2006;27(25):4419–27.

    Article  CAS  Google Scholar 

  10. Nakamura T. Biomaterial osteoinduction. J Orthop Sci. 2007;12(2):111–2.

    Article  Google Scholar 

  11. Ripamonti U. Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials. 1996;17(1):31–5.

    Article  CAS  Google Scholar 

  12. Yuan H, Kurashina K, de Bruijn JD, Li Y, de Groot K, Zhang X. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials. 1999;20(19):1799–806.

    Article  CAS  Google Scholar 

  13. El-Ghannam A. Bone reconstruction: from bioceramics to tissue engineering. Expert Rev Med Devices. 2005;2(1):87–101.

    Article  Google Scholar 

  14. Gauthier O, Bouler JM, Aguado E, Pilet P, Daculsi G. Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. Biomaterials. 1998;19(1–3):133–9.

    Article  CAS  Google Scholar 

  15. Hollister SJ, Maddox RD, Taboas JM. Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. Biomaterials. 2002;23(20):4095–103.

    Article  CAS  Google Scholar 

  16. Hunt JA. Regenerative medicine: materials in a cellular world. Nat Mater. 2008;7(8):617–8.

    Article  CAS  Google Scholar 

  17. Hutmacher DW. Scaffolds in tissue engineering bone and cartilage. Biomaterials. 2000;21(24):2529–43.

    Article  CAS  Google Scholar 

  18. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26(27):5474–91.

    Article  CAS  Google Scholar 

  19. Liu X, Ma PX. Polymeric scaffolds for bone tissue engineering. Ann Biomed Eng. 2004;32(3):477–86.

    Article  Google Scholar 

  20. Mastrogiacomo M, Scaglione S, Martinetti R, Dolcini L, Beltrame F, Cancedda R, et al. Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics. Biomaterials. 2006;27(17):3230–7.

    Article  CAS  Google Scholar 

  21. Ishaug-Riley SL, Crane-Kruger GM, Yaszemski MJ, Mikos AG. Three-dimensional culture of rat calvarial osteoblasts in porous biodegradable polymers. Biomaterials. 1998;19(15):1405–12.

    Article  CAS  Google Scholar 

  22. Roy TD, Simon JL, Ricci JL, Rekow ED, Thompson VP, Parsons JR. Performance of degradable composite bone repair products made via three-dimensional fabrication techniques. J Biomed Mater Res A. 2003;66(2):283–91.

    Article  Google Scholar 

  23. Guarino V, Causa F, Salerno A, Ambrosio L, Netti PA. Design and manufacture of microporous polymeric materials with hierarchal complex structure for biomedical application. Mater Sci Technol. 2008;24(9):1111–7.

    Article  CAS  Google Scholar 

  24. Guarino V, Guaccio A, Guarnieri D, Netti PA, Ambrosio L. Binary system thermodynamics to control pore architecture of PCL scaffold via temperature-driven phase separation process. J Biomater Appl; 2011.

  25. Lee J, Guarino V, Gloria A, Ambrosio L, Tae G, Kim YH, et al. Regeneration of Achilles’ tendon: the role of dynamic stimulation for enhanced cell proliferation and mechanical properties. J Biomater Sci Polym Ed. 2010;21(8–9):1173–90.

    Article  CAS  Google Scholar 

  26. Chim H, Hutmacher DW, Chou AM, Oliveira AL, Reis RL, Lim TC, et al. A comparative analysis of scaffold material modifications for load-bearing applications in bone tissue engineering. Int J Oral Maxillofac Surg. 2006;35(10):928–34.

    Article  CAS  Google Scholar 

  27. Zhao J, Guo LY, Yang XB, Weng J. Preparation of bioactive porous HA/PCL composite scaffolds. Appl Surf Sci. 2008;255(5):2942–6.

    Article  CAS  Google Scholar 

  28. Guarino V, Causa F, Netti PA, Ciapetti G, Pagani S, Martini D, et al. The role of hydroxyapatite as solid signal on performance of PCL porous scaffolds for bone tissue regeneration. J Biomed Mater Res B Appl Biomater. 2008;86B(2):548–57.

    Article  CAS  Google Scholar 

  29. Scaglione S, Ilengo C, Fato M, Quarto R. Hydroxyapatite-coated polycaprolacton wide mesh as a model of open structure for bone regeneration. Tissue Eng Part A. 2009;15(1):155–63.

    Article  CAS  Google Scholar 

  30. Causa F, Netti PA, Ambrosio L. A multi-functional scaffold for tissue regeneration: the need to engineer a tissue analogue. Biomaterials. 2007;28(34):5093–9.

    Article  CAS  Google Scholar 

  31. Ma PX. Biomimetic materials for tissue engineering. Adv Drug Deliv Rev. 2008;60(2):184–98.

    Article  CAS  Google Scholar 

  32. Elliott JC. Structure and chemistry of the apatites and other calcium orthophosphates, studies in inorganic chemistry, vol. 18. Amsterdam: Elsevier; 1994.

  33. Termine JD, Eanes ED. Comparative chemistry of amorphous and apatitic calcium phosphate preparations. Calcif Tissue Res. 1972;10(3):171–97.

    Article  CAS  Google Scholar 

  34. Heaney RP. Role of dietary sodium in osteoporosis. J Am Coll Nutr. 2006;25(3 Suppl):271S–6S.

    CAS  Google Scholar 

  35. Landi E, Logroscino G, Proietti L, Tampieri A, Sandri M, Sprio S. Biomimetic Mg-substituted hydroxyapatite: from synthesis to in vivo behaviour. J Mater Sci Mater Med. 2008;19(1):239–47.

    Article  CAS  Google Scholar 

  36. Dasgupta S, Banerjee SS, Bandyopadhyay A, Bose S. Zn- and Mg-doped hydroxyapatite nanoparticles for controlled release of protein. Langmuir. 2010;26(7):4958–64.

    Article  CAS  Google Scholar 

  37. Desai TA. Micro- and nanoscale structures for tissue engineering constructs. Med Eng Phys. 2000;22(9):595–606.

    Article  CAS  Google Scholar 

  38. Kretlow JD, Mikos AG. Review: mineralization of synthetic polymer scaffolds for bone tissue engineering. Tissue Eng. 2007;13(5):927–38.

    Article  CAS  Google Scholar 

  39. Lim JY, Dreiss AD, Zhou Z, Hansen JC, Siedlecki CA, Hengstebeck RW, et al. The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion kinase expression by nanoscale topography. Biomaterials. 2007;28(10):1787–97.

    Article  CAS  Google Scholar 

  40. Pham QP, Sharma U, Mikos AG. Electrospun poly(epsilon-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules. 2006;7(10):2796–805.

    Article  CAS  Google Scholar 

  41. Stevens MM, George JH. Exploring and engineering the cell surface interface. Science. 2005;310(5751):1135–8.

    Article  CAS  Google Scholar 

  42. Balasundaram G, Webster TJ. An overview of nano-polymers for orthopedic applications. Macromol Biosci. 2007;7(5):635–42.

    Article  CAS  Google Scholar 

  43. Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL. Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev. 2007;59(14):1413–33.

    Article  CAS  Google Scholar 

  44. Christenson EM, Anseth KS, van den Beucken JJ, Chan CK, Ercan B, Jansen JA, et al. Nanobiomaterial applications in orthopedics. J Orthop Res. 2007;25(1):11–22.

    Article  CAS  Google Scholar 

  45. Chun YW, Webster TJ. The role of nanomedicine in growing tissues. Ann Biomed Eng. 2009;37(10):2034–47.

    Article  Google Scholar 

  46. Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6(12):997–1003.

    Article  CAS  Google Scholar 

  47. Jayaraman K, Kotaki M, Zhang Y, Mo X, Ramakrishna S. Recent advances in polymer nanofibers. J Nanosci Nanotechnol. 2004;4(1–2):52–65.

    CAS  Google Scholar 

  48. Smith LA, Liu X, Ma PX. Tissue engineering with nano-fibrous scaffolds. Soft Matter. 2008;4(11):2144–9.

    Article  CAS  Google Scholar 

  49. Wei G, Ma P. Nanostructured biomaterials for regeneration. Adv Funct Mater. 2008;18:3568–82.

    Article  CAS  Google Scholar 

  50. Teo WE, He W, Ramakrishna S. Electrospun scaffold tailored for tissue-specific extracellular matrix. Biotechnol J. 2006;1(9):918–29.

    Article  CAS  Google Scholar 

  51. Ma Z, Kotaki M, Inai R, Ramakrishna S. Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng. 2005;11(1–2):101–9.

    Article  Google Scholar 

  52. Nisbet DR, Pattanawong S, Ritchie NE, Shen W, Finkelstein DI, Horne MK, et al. Interaction of embryonic cortical neurons on nanofibrous scaffolds for neural tissue engineering. J Neural Eng. 2007;4(2):35–41.

    Article  CAS  Google Scholar 

  53. Guarino V, Taddei P, Di Foggia M, Fagnano C, Ciapetti G, Ambrosio L. The influence of hydroxyapatite particles on in vitro degradation behavior of poly epsilon-caprolactone-based composite scaffolds. Tissue Eng Part A. 2009;15(11):3655–68.

    Article  CAS  Google Scholar 

  54. Theron SA, Zussman E, Yarin AL. Experimental investigation of the governing parameters in the electrospinning of polymer solutions. Polymer. 2004;45(6):2017–30.

    Article  CAS  Google Scholar 

  55. Muraglia A, Martin I, Cancedda R, Quarto R. A nude mouse model for human bone formation in unloaded conditions. Bone. 1998;22(5 Suppl):131S–4S.

    Article  CAS  Google Scholar 

  56. Anselme K, Noel B, Flautre B, Blary MC, Delecourt C, Descamps M, et al. Association of porous hydroxyapatite and bone marrow cells for bone regeneration. Bone. 1999;25(2 Suppl):51S–4S.

    Article  CAS  Google Scholar 

  57. Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I, et al. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res. 2000;49(3):328–37.

    Article  CAS  Google Scholar 

  58. Nishikawa M, Myoui A, Ohgushi H, Ikeuchi M, Tamai N, Yoshikawa H. Bone tissue engineering using novel interconnected porous hydroxyapatite ceramics combined with marrow mesenchymal cells: quantitative and three-dimensional image analysis. Cell Transpl. 2004;13(4):367–76.

    Article  Google Scholar 

  59. Thorwarth M, Schultze-Mosgau S, Kessler P, Wiltfang J, Schlegel KA. Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite. J Oral Maxillofac Surg. 2005;63(11):1626–33.

    Article  Google Scholar 

  60. Yoshikawa H, Myoui A. Bone tissue engineering with porous hydroxyapatite ceramics. J Artif Organs. 2005;8(3):131–6.

    Article  CAS  Google Scholar 

  61. Arinzeh TL, Tran T, McAlary J, Daculsi G. A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation. Biomaterials. 2005;26(17):3631–8.

    Article  CAS  Google Scholar 

  62. Kasten P, Luginbuhl R, van Griensven M, Barkhausen T, Krettek C, Bohner M, et al. Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapatite, beta-tricalcium phosphate and demineralized bone matrix. Biomaterials. 2003;24(15):2593–603.

    Article  CAS  Google Scholar 

  63. Ohgushi H, Dohi Y, Tamai S, Tabata S. Osteogenic differentiation of marrow stromal stem cells in porous hydroxyapatite ceramics. J Biomed Mater Res. 1993;27(11):1401–7.

    Article  CAS  Google Scholar 

  64. Dekker RJ, de Bruijn JD, Stigter M, Barrere F, Layrolle P, van Blitterswijk CA. Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs. Biomaterials. 2005;26(25):5231–9.

    Article  CAS  Google Scholar 

  65. Landi E, Sprio S, Sandri M, Celotti G, Tampieri A. Development of Sr and CO3 co-substituted hydroxyapatites for biomedical applications. Acta Biomater. 2008;4(3):656–63.

    Article  CAS  Google Scholar 

  66. Tan J, Saltzman WM. Biomaterials with hierarchically defined micro- and nanoscale structure. Biomaterials. 2004;25(17):3593–601.

    Article  CAS  Google Scholar 

  67. Mendonca G, Mendonca DB, Simoes LG, Araujo AL, Leite ER, Duarte WR, et al. The effects of implant surface nanoscale features on osteoblast-specific gene expression. Biomaterials. 2009;30(25):4053–62.

    Article  CAS  Google Scholar 

  68. Webster TJ, Ergun C, Doremus RH, Siegel RW, Bizios R. Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics. J Biomed Mater Res. 2000;51(3):475–83.

    Article  CAS  Google Scholar 

  69. Biggs MJ, Richards RG, Gadegaard N, Wilkinson CD, Oreffo RO, Dalby MJ. The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+ enriched skeletal stem cells. Biomaterials. 2009;30(28):5094–103.

    Article  CAS  Google Scholar 

  70. James R, Toti US, Laurencin CT, Kumbar SG. Electrospun nanofibrous scaffolds for engineering soft connective tissues. Methods Mol Biol. 2011;726:243–58.

    Article  CAS  Google Scholar 

  71. Vasita R, Katti DS. Nanofibers and their applications in tissue engineering. Int J Nanomed. 2006;1(1):15–30.

    Article  CAS  Google Scholar 

  72. Curtis AS, Dalby M, Gadegaard N. Cell signaling arising from nanotopography: implications for nanomedical devices. Nanomedicine (Lond). 2006;1(1):67–72.

    Article  CAS  Google Scholar 

  73. Schenk S, Quaranta V. Tales from the crypt[ic] sites of the extracellular matrix. Trends Cell Biol. 2003;13(7):366–75.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors Silvia Scaglione and Vincenzo Guarino contributed equally to this paper. This paper was supported by Italian research project FIRB TISSUENET (Prot. N. RBPR05RSM2). Scanning electron Microscopy was supported by the Transmission and Scanning Electron Microscopy Labs (LAMEST) on the National Research Council.

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Authors and Affiliations

  1. CNR-National Research Council of Italy, IEIIT Institute, Genoa, Italy

    Silvia Scaglione

  2. National Research Council (CNR), Institute of Composite and Biomedical Materials (IMCB), Naples, Italy

    Vincenzo Guarino & Luigi Ambrosio

  3. CNR-National Research Council of Italy, Institute of Science and Technology for Ceramic Materials (ISTEC), Faenza, Italy

    Monica Sandri & Anna Tampieri

  4. Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy

    Rodolfo Quarto

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  1. Silvia Scaglione
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  2. Vincenzo Guarino
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  3. Monica Sandri
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  4. Anna Tampieri
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  5. Luigi Ambrosio
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Correspondence to Silvia Scaglione or Vincenzo Guarino.

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Scaglione, S., Guarino, V., Sandri, M. et al. In vivo lamellar bone formation in fibre coated MgCHA–PCL-composite scaffolds. J Mater Sci: Mater Med 23, 117–128 (2012). https://doi.org/10.1007/s10856-011-4489-y

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