dc.contributor.author
Pfeiffenberger, Moritz
dc.contributor.author
Damerau, Alexandra
dc.contributor.author
Ponomarev, Igor
dc.contributor.author
Bucher, Christian H
dc.contributor.author
Chen, Yuling
dc.contributor.author
Barnewitz, Dirk
dc.contributor.author
Thöne‐Reineke, Christa
dc.contributor.author
Hoff, Paula
dc.contributor.author
Buttgereit, Frank
dc.contributor.author
Gaber, Timo
dc.contributor.author
Lang, Annemarie
dc.date.accessioned
2022-11-28T13:36:50Z
dc.date.available
2022-11-28T13:36:50Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/37054
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-36768
dc.description.abstract
After trauma, the formed fracture hematoma within the fracture gap contains all the important components (immune/stem cells, mediators) to initiate bone regeneration immediately. Thus, it is of great importance but also the most susceptible to negative influences. To study the interaction between bone and immune cells within the fracture gap, up-to-date in vitro systems should be capable of recapitulating cellular and humoral interactions and the physicochemical microenvironment (eg, hypoxia). Here, we first developed and characterized scaffold-free bone-like constructs (SFBCs), which were produced from bone marrow-derived mesenchymal stromal cells (MSCs) using a macroscale mesenchymal condensation approach. SFBCs revealed permeating mineralization characterized by increased bone volume (mu CT, histology) and expression of osteogenic markers (RUNX2, SPP1, RANKL). Fracture hematoma (FH) models, consisting of human peripheral blood (immune cells) mixed with MSCs, were co-cultivated with SFBCs under hypoxic conditions. As a result, FH models revealed an increased expression of osteogenic (RUNX2, SPP1), angiogenic (MMP2, VEGF), HIF-related (LDHA, PGK1), and inflammatory (IL6, IL8) markers after 12 and 48 hours co-cultivation. Osteogenic and angiogenic gene expression of the FH indicate the osteoinductive potential and, thus, the biological functionality of the SFBCs. IL-6, IL-8, GM-CSF, and MIP-1 beta were detectable within the supernatant after 24 and 48 hours of co-cultivation. To confirm the responsiveness of our model to modifying substances (eg, therapeutics), we used deferoxamine (DFO), which is well known to induce a cellular hypoxic adaptation response. Indeed, DFO particularly increased hypoxia-adaptive, osteogenic, and angiogenic processes within the FH models but had little effect on the SFBCs, indicating different response dynamics within the co-cultivation system. Therefore, based on our data, we have successfully modeled processes within the initial fracture healing phase in vitro and concluded that the cross-talk between bone and immune cells in the initial fracture healing phase is of particular importance for preclinical studies. (c) 2021 American Society for Bone and Mineral Research (ASBMR).
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
BIOENGINEERING
en
dc.subject
FRACTURE HEALING
en
dc.subject
FRACTURE HEMATOMA
en
dc.subject
OSTEOIMMUNOLOGY
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Functional Scaffold‐Free Bone Equivalents Induce Osteogenic and Angiogenic Processes in a Human In Vitro Fracture Hematoma Model
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1002/jbmr.4267
dcterms.bibliographicCitation.journaltitle
Journal of Bone and Mineral Research
dcterms.bibliographicCitation.number
6
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
1189
dcterms.bibliographicCitation.pageend
1201
dcterms.bibliographicCitation.volume
36
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33534144
dcterms.isPartOf.issn
0884-0431
dcterms.isPartOf.eissn
1523-4681