Functional Scaffold?Free Bone Equivalents Induce Osteogenic and Angiogenic Processes in a Human In Vitro Fracture Hematoma Model

After trauma, the formed fracture hematoma within gap contains all important components (immune/stem cells, mediators) to initiate bone regeneration immediately. Thus, it is of great importance but also most susceptible negative influences. To study interaction between and immune cells gap, up-to-date in vitro systems should be capable recapitulating cellular humoral interactions physicochemical microenvironment (eg, hypoxia). Here, we first developed characterized scaffold-free bone-like constructs (SFBCs), which were produced from marrow-derived mesenchymal stromal (MSCs) using a macroscale condensation approach. SFBCs revealed permeating mineralization by increased volume (?CT, histology) expression osteogenic markers (RUNX2, SPP1, RANKL). Fracture (FH) models, consisting human peripheral blood (immune cells) mixed with MSCs, co-cultivated under hypoxic conditions. As result, FH models an SPP1), angiogenic (MMP2, VEGF), HIF-related (LDHA, PGK1), inflammatory (IL6, IL8) after 12 48?hours co-cultivation. Osteogenic gene indicate osteoinductive potential and, thus, biological functionality SFBCs. IL-6, IL-8, GM-CSF, MIP-1? detectable supernatant 24 confirm responsiveness our model modifying substances therapeutics), used deferoxamine (DFO), well known induce adaptation response. Indeed, DFO particularly hypoxia-adaptive, osteogenic, processes had little effect on SFBCs, indicating different response dynamics co-cultivation system. Therefore, based data, have successfully modeled initial healing phase concluded that cross-talk particular for preclinical studies. © 2021 American Society Bone Mineral Research (ASBMR).