Synthesis and physicochemical, in vitro and in vivo evaluation of an anisotropic, nanocrystalline hydroxyapatite bisque scaffold with parallel-aligned pores mimicking the microstructure of cortical bone

J Tissue Eng Regen Med. 2015 Dec;9(12):E152-66. doi: 10.1002/term.1729. Epub 2013 Apr 15.

Abstract

Scaffolds for bone regeneration are mostly prepared with an isotropic, sponge-like structure mimicking the architecture of trabecular bone. We have developed an anisotropic bioceramic with parallel aligned pores resembling the honeycomb arrangement of Haversian canals of cortical bone and investigated its potential as a scaffold for tissue engineering. Parallel channel-like pores were generated by ionotropic gelation of an alginate-hydroxyapatite (HA) slurry, followed by ceramic processing. Organic components were thermally removed at 650 °C, whereas the pore system was preserved in the obtained HA bioceramic in the processing stage of a bisque. Even without further sintering at higher temperatures, the anisotropic HA bisque (AHAB) became mechanically stable with a compressive strength (4.3 MPa) comparable to that of native trabecular bone. Owing to the low-temperature treatment, a nanocrystalline microstructure with high porosity (82%) and surface area (24.9 m(2)/g) was achieved that kept the material dissolvable in acidic conditions, similar to osteoclastic degradation of bone. Human mesenchymal stem cells (hMSCs) adhered, proliferated and differentiated into osteoblasts when osteogenically induced, indicating the cytocompatibility of the bisque scaffold. Furthermore, we demonstrated fusion of human monocytes to osteoclast-like cells in vitro on this substrate, similar to the natural pathway. Biocompatibility was demonstrated in vivo by implantation of the bisque ceramic into cortical rabbit femur defects, followed by histological analysis, where new bone formation inside the channel-like pores and generation of an osteon-like tissue morphology was observed.

Keywords: anisotropic scaffold; biomimetic material; bone tissue engineering; cytocompatibility; femoral defect; human mesenchymal stem cells; ionotropic gelation of alginate; nanocrystalline apatite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisotropy
  • Bone Substitutes* / chemistry
  • Bone Substitutes* / pharmacology
  • Cell Differentiation / drug effects
  • Durapatite* / chemistry
  • Durapatite* / pharmacology
  • Female
  • Femur / chemistry
  • Femur / metabolism*
  • Femur / pathology
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Nanoparticles / chemistry*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteogenesis / drug effects
  • Porosity
  • Rabbits
  • Tissue Scaffolds / chemistry*

Substances

  • Bone Substitutes
  • Durapatite