Hydroxyapatite nanoparticle-containing scaffolds for the study of breast cancer bone metastasis

Biomaterials. 2011 Aug;32(22):5112-22. doi: 10.1016/j.biomaterials.2011.03.055. Epub 2011 Apr 20.


Breast cancer frequently metastasizes to bone, where it leads to secondary tumor growth, osteolytic bone degradation, and poor clinical prognosis. Hydroxyapatite Ca(10)(PO(4))(6)(OH)(2) (HA), a mineral closely related to the inorganic component of bone, may be implicated in these processes. However, it is currently unclear how the nanoscale materials properties of bone mineral, such as particle size and crystallinity, which change as a result of osteolytic bone remodeling, affect metastatic breast cancer. We have developed a two-step hydrothermal synthesis method to obtain HA nanoparticles with narrow size distributions and varying crystallinity. These nanoparticles were incorporated into gas-foamed/particulate leached poly(lactide-co-glycolide) scaffolds, which were seeded with metastatic breast cancer cells to create mineral-containing scaffolds for the study of breast cancer bone metastasis. Our results suggest that smaller, poorly-crystalline HA nanoparticles promote greater adsorption of adhesive serum proteins and enhance breast tumor cell adhesion and growth relative to larger, more crystalline nanoparticles. Conversely, the larger, more crystalline HA nanoparticles stimulate enhanced expression of the osteolytic factor interleukin-8 (IL-8). Our data suggest an important role for nanoscale HA properties in the vicious cycle of bone metastasis and indicate that mineral-containing tumor models may be excellent tools to study cancer biology and to define design parameters for non-tumorigenic mineral-containing or mineralized matrices for bone regeneration.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary*
  • Bone and Bones / pathology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Durapatite / chemistry*
  • Female
  • Humans
  • Interleukin-8 / metabolism
  • Materials Testing
  • Nanoparticles / chemistry*
  • Neoplasm Metastasis
  • Particle Size
  • Tissue Scaffolds / chemistry*
  • Tumor Cells, Cultured
  • X-Ray Diffraction


  • Interleukin-8
  • Durapatite