Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells

A Diez-Escudero, E Torreggiani, Gemma Di Pompo, M Espanol, C Persson, Gabriela Ciapetti, Nicola Baldini, M-P Ginebra

Research output: Contribution to journalArticlepeer-review

Abstract

The immobilization of natural molecules on synthetic bone grafts stands as a strategy to enhance their biological interactions. During the early stages of healing, immune cells and osteoclasts (OC) modulate the inflammatory response and resorb the biomaterial, respectively. In this study, heparin, a naturally occurring molecule in the bone extracellular matrix, was covalently immobilized on biomimetic calcium-deficient hydroxyapatite (CDHA). The effect of heparin-functionalized CDHA on inflammation and osteoclastogenesis was investigated using primary human cells, and compared to pristine CDHA and beta-tricalcium phosphate (β-TCP). Biomimetic substrates led to lower oxidative stresses by neutrophils and monocytes than sintered β-TCP, even though no further reduction was induced by the presence of heparin. In contrast, heparinized CDHA fostered osteoclastogenesis. Optical images of stained TRAP positive cells showed an earlier and higher presence of multinucleated cells, compatible with OC at 14 days, whilst pristine CDHA and β-TCP present OC at 21-28 days. Although no statistically significant differences were found in the OC activity, microscopy images evidenced early stages of degradation on heparinized CDHA, compatible with osteoclastic resorption. Overall, the results suggest that the functionalization with heparin fostered the formation and activity of OC, thus offering a promising strategy to integrate biomaterials in the bone remodeling cycle by increasing their OC-mediated resorption.

Original languageEnglish
Pages (from-to)1217-1229
Number of pages13
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume13
Issue number7
Early online dateMay 3 2019
DOIs
Publication statusPublished - Jul 2019

Keywords

  • Biomaterial
  • heparin
  • hydroxyapatite
  • inflammation
  • osteoclastogenesis

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