Correlation between Ca Release and Osteoconduction by 3D-Printed Hydroxyapatite-Based Templates

ACS Appl Mater Interfaces. 2024 Jun 5;16(22):28056-28069. doi: 10.1021/acsami.4c01472. Epub 2024 May 25.


The application of hydroxyapatite (HA)-based templates is quite often seen in bone tissue engineering since that HA is an osteoconductive bioceramic material, which mimics the inorganic component of mineralized tissues. However, the reported osteoconductivity varies in vitro and in vivo, and the levels of calcium (Ca) release most favorable to osteoconduction have yet to be determined. In this study, HA-based templates were fabricated by melt-extrusion 3D-printing and characterized in order to determine a possible correlation between Ca release and osteoconduction. The HA-based templates were blended with poly(lactide-co-trimethylene carbonate) (PLATMC) at three different HA ratios: 10, 30, and 50%. The printability and physical properties of the HA templates were compared with those of pristine PLATMC. In vitro, osteoconductivity was assessed using seeded human bone marrow-derived mesenchymal stem cells. A mild rate of Ca release was observed for HA10 templates, which exhibited higher mineralized extracellular matrix (ECM) secretion than PLATMC at 14 and 21 days. In contrast, the high rate of Ca release exhibited by HA30 and HA50 templates was associated with reduced osteoconduction and impeded mineralized ECM secretion in vitro. Similar results were observed in vivo. In the calvarial defect model in rabbit, PLATMC and HA10 templates exhibited the highest amount of new bone formation, with obvious contact osteogenesis on their surfaces. In contrast, HA30 and HA50 exhibited distant osteogenesis and reduced amounts of new bone ingrowth. It is concluded that HA-based templates are osteoconductive only at low rates of Ca release.

Keywords: PLATMC; blending; bone regeneration; calcium phosphates; calvarial bone defect; printability; rabbit.

MeSH terms

  • Animals
  • Bone Regeneration* / drug effects
  • Calcium* / chemistry
  • Calcium* / metabolism
  • Durapatite* / chemistry
  • Humans
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Osteogenesis / drug effects
  • Printing, Three-Dimensional*
  • Rabbits
  • Tissue Engineering
  • Tissue Scaffolds / chemistry


  • Durapatite
  • Calcium