Low-Temperature Additive Manufacturing of Biomimic Three-Dimensional Hydroxyapatite/Collagen Scaffolds for Bone Regeneration

ACS Appl Mater Interfaces. 2016 Mar 23;8(11):6905-16. doi: 10.1021/acsami.6b00815. Epub 2016 Mar 9.


Low-temperature additive manufacturing (AM) holds promise for fabrication of three-dimensional (3D) scaffolds containing bioactive molecules and/or drugs. Due to the strict technical limitations of current approaches, few materials are suitable for printing at low temperature. Here, a low-temperature robocasting method was employed to print biomimic 3D scaffolds for bone regeneration using a routine collagen-hydroxyapatite (CHA) composite material, which is too viscous to be printed via normal 3D printing methods at low temperature. The CHA scaffolds had excellent 3D structure and maintained most raw material properties after printing. Compared to nonprinted scaffolds, printed scaffolds promoted bone marrow stromal cell proliferation and improved osteogenic outcome in vitro. In a rabbit femoral condyle defect model, the interconnecting pores within the printed scaffolds facilitated cell penetration and mineralization before the scaffolds degraded and enhanced repair, compared to nonprinted CHA scaffolds. Additionally, the optimal printing parameters for 3D CHA scaffolds were investigated; 600-μm-diameter rods were optimal in terms of moderate mechanical strength and better repair outcome in vivo. This low-temperature robocasting method could enable a variety of bioactive molecules to be incorporated into printed CHA materials and provides a method of bioprinting biomaterials without compromising their natural properties.

Keywords: bone substitutes; collagen; hydroxyapatite; three-dimensional printing; tissue engineering.

MeSH terms

  • Animals
  • Biomimetic Materials* / chemistry
  • Biomimetic Materials* / pharmacology
  • Bone Marrow Cells / metabolism
  • Bone Regeneration / drug effects*
  • Bone Substitutes / pharmacology*
  • Cattle
  • Cell Proliferation
  • Cells, Cultured
  • Collagen* / chemistry
  • Collagen* / pharmacology
  • Durapatite* / chemistry
  • Durapatite* / pharmacology
  • Femur* / injuries
  • Femur* / metabolism
  • Femur* / pathology
  • Male
  • Rabbits
  • Stromal Cells / metabolism
  • Tissue Scaffolds / chemistry*


  • Bone Substitutes
  • Collagen
  • Durapatite