SiO2 and ZnO dopants in three-dimensionally printed tricalcium phosphate bone tissue engineering scaffolds enhance osteogenesis and angiogenesis in vivo

Acta Biomater. 2013 Nov;9(11):9137-48. doi: 10.1016/j.actbio.2013.07.009. Epub 2013 Jul 18.


Calcium phosphate (CaP) scaffolds with three-dimensionally-interconnected pores play an important role in mechanical interlocking and biological fixation in bone implant applications. CaPs alone, however, are only osteoconductive (able to guide bone growth). Much attention has been given to the incorporation of biologics and pharmacologics to add osteoinductive (able to cause new bone growth) properties to CaP materials. Because biologics and pharmacologics are generally delicate compounds and also subject to increased regulatory scrutiny, there is a need to investigate alternative methods to introduce osteoinductivity to CaP materials. In this study silica (SiO2) and zinc oxide (ZnO) have been incorporated into three-dimensional printed β-tricalcium phosphate (β-TCP) scaffolds to investigate their potential to trigger osteoinduction in vivo. Silicon and zinc are trace elements that are common in bone and have also been shown to have many beneficial properties, from increased bone regeneration to angiogenesis. Implants were placed in bicortical femur defects introduced to a murine model for up to 16 weeks. The addition of dopants into TCP increased the capacity for new early bone formation by modulating collagen I production and osteocalcin production. Neovascularization was found to be up to three times more than the pure TCP control group. The findings from this study indicate that the combination of SiO2 and ZnO dopants in TCP may be a viable alternative to introducing osteoinductive properties to CaPs.

Keywords: 3-D printing; Bone tissue engineering; Calcium phosphate; Dopants; Scaffold.

Publication types

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

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Blood Vessels / drug effects
  • Blood Vessels / growth & development
  • Blood Vessels / ultrastructure
  • Bone and Bones / drug effects
  • Bone and Bones / physiology*
  • Calcium Phosphates / pharmacology*
  • Collagen Type I / metabolism
  • Implants, Experimental
  • Ions / urine
  • Isoenzymes / metabolism
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Osteocalcin / metabolism
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Printing
  • Rats
  • Rats, Sprague-Dawley
  • Silicon Dioxide / pharmacology*
  • Tartrate-Resistant Acid Phosphatase
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry
  • Zinc Oxide / pharmacology*


  • Calcium Phosphates
  • Collagen Type I
  • Ions
  • Isoenzymes
  • Osteocalcin
  • Silicon Dioxide
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • tricalcium phosphate
  • Zinc Oxide