Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

Harvestine, J. N.; Gonzalez-Fernandez, T.; Sebastian, A.; Hum, N. R.; Genetos, D. C.; Loots, G. G.; Leach, J. K.

doi:10.1126/sciadv.aay2387

Title: Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

Journal Article · Wed Feb 12 00:00:00 EST 2020 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aay2387· OSTI ID:1626036

^[1]; Gonzalez-Fernandez, T. ^[1]; Sebastian, A. ^[2]; Hum, N. R. ^[3];

^[4]; Loots, G. G. ^[3];

^[5]

Univ. of California, Davis, CA (United States). Dept. of Biomedical Engineering
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences
Univ. of California, Davis, CA (United States). Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine
Univ. of California, Davis, CA (United States). Dept. of Biomedical Engineering; UC Davis Health, Sacramento, California (United States). Department of Orthopaedic Surgery, School of Medicine

Cell-derived extracellular matrix (ECM) provides a niche to promote osteogenic differentiation, cell adhesion, survival, and trophic factor secretion. To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), we perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs, respectively. The composition of cells selected from BMA was distinct on each scaffold. Naïve constructs exhibited robust proangiogenic potential in vitro, while preconditioned scaffolds contained more mesenchymal stem/stromal cells (MSCs) and endothelial cells (ECs) and exhibited an osteogenic phenotype. Upon implantation into an orthotopic calvarial defect, BMA-derived ECs were present in vessels in preconditioned implants, resulting in robust perfusion and greater vessel density over the first 14 days compared to naïve implants. After 10 weeks, human ECs and differentiated MSCs were detected in de novo tissues derived from naïve and preconditioned scaffolds. These results demonstrate that bioreactor-based preconditioning augments the bone-forming potential of BMA.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1626036

Alternate ID(s):: OSTI ID: 1755844

Report Number(s):: LLNL-JRNL-789381

Journal Information:: Science Advances, Vol. 6, Issue 7; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
extracellular matrix
bone marrow aspirate
bioreactor
osteogenesis
vascularization

Title: Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

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