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Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells
UPC, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 16, Barcelona 08019, Spain;UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona, Spain.ORCID iD: 0000-0003-4686-9564
IRCCS Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy.
IRCCS Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy.
UPC, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 16, Barcelona 08019, Spain;UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona, Spain.
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2019 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 13, no 7, p. 1217-1229Article in journal (Refereed) Published
Abstract [en]

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 (beta-TCP). Biomimetic substrates led to lower oxidative stresses by neutrophils and monocytes than sintered beta-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 beta-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.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 13, no 7, p. 1217-1229
Keywords [en]
biomaterial, heparin, hydroxyapatite, inflammation, osteoclastogenesis
National Category
Materials Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-391031DOI: 10.1002/term.2872ISI: 000475495400011PubMedID: 31050382OAI: oai:DiVA.org:uu-391031DiVA, id: diva2:1343652
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), STINT-IG2011-2047Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-08-19Bibliographically approved

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Persson, Cecilia

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