Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells.
Anna Diez-EscuderoElena TorreggianiGemma Di PompoMontserrat EspanolCecilia PerssonGabriela CiapettiNicola BaldiniMaria-Pau GinebraPublished in: Journal of tissue engineering and regenerative medicine (2019)
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 with 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, while 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 remodelling cycle by increasing their OC-mediated resorption.
Keyphrases
- bone loss
- inflammatory response
- induced apoptosis
- cell cycle arrest
- bone regeneration
- extracellular matrix
- venous thromboembolism
- lps induced
- bone mineral density
- oxidative stress
- growth factor
- deep learning
- endoplasmic reticulum stress
- convolutional neural network
- cell death
- soft tissue
- machine learning
- magnetic resonance imaging
- high speed
- quantum dots
- single molecule
- mass spectrometry
- immune response
- high throughput
- cell proliferation
- peripheral blood
- induced pluripotent stem cells