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Open AccessArticle

In Vitro Prevascularization of Self-Assembled Human Bone-Like Tissues and Preclinical Assessment Using a Rat Calvarial Bone Defect Model

1
Centre de Recherche en Organogénèse Expérimentale de l′Université Laval/LOEX, Division of Regenerative Medicine, CHU de Québec Research Center-Université Laval, Québec, QC G1J 1Z4, Canada
2
Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada
3
Faculty of Dentistry, Université Laval, Québec, QC G1V 0A6, Canada
4
Service of Oral and Maxillofacial Surgery, CHU de Québec-Université Laval, Québec, QC G1J 1Z4, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Barbara Rothen-Rutishauser, Alke Petri-Fink, Barbara Drasler and Dedy Septiadi
Materials 2021, 14(8), 2023; https://doi.org/10.3390/ma14082023
Received: 28 March 2021 / Revised: 14 April 2021 / Accepted: 15 April 2021 / Published: 17 April 2021
(This article belongs to the Special Issue Advances in Bio-Inspired Materials for Medical Applications)
In vitro prevascularization has the potential to address the challenge of maintaining cell viability at the core of engineered constructs, such as bone substitutes, and to improve the survival of tissue grafts by allowing quicker anastomosis to the host microvasculature. The self-assembly approach of tissue engineering allows the production of biomimetic bone-like tissue constructs including extracellular matrix and living human adipose-derived stromal/stem cells (hASCs) induced towards osteogenic differentiation. We hypothesized that the addition of endothelial cells could improve osteogenesis and biomineralization during the production of self-assembled human bone-like tissues using hASCs. Additionally, we postulated that these prevascularized constructs would consequently improve graft survival and bone repair of rat calvarial bone defects. This study shows that a dense capillary network spontaneously formed in vitro during tissue biofabrication after two weeks of maturation. Despite reductions in osteocalcin levels and hydroxyapatite formation in vitro in prevascularized bone-like tissues (35 days of culture), in vivo imaging of prevascularized constructs showed an improvement in cell survival without impeding bone healing after 12 weeks of implantation in a calvarial bone defect model (immunocompromised male rats), compared to their stromal counterparts. Globally, these findings establish our ability to engineer prevascularized bone-like tissues with improved functional properties. View Full-Text
Keywords: prevascularization; mesenchymal stem cells; calvarial bone defect; self-assembly; endothelial; adipose prevascularization; mesenchymal stem cells; calvarial bone defect; self-assembly; endothelial; adipose
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MDPI and ACS Style

Kawecki, F.; Galbraith, T.; Clafshenkel, W.P.; Fortin, M.; Auger, F.A.; Fradette, J. In Vitro Prevascularization of Self-Assembled Human Bone-Like Tissues and Preclinical Assessment Using a Rat Calvarial Bone Defect Model. Materials 2021, 14, 2023. https://doi.org/10.3390/ma14082023

AMA Style

Kawecki F, Galbraith T, Clafshenkel WP, Fortin M, Auger FA, Fradette J. In Vitro Prevascularization of Self-Assembled Human Bone-Like Tissues and Preclinical Assessment Using a Rat Calvarial Bone Defect Model. Materials. 2021; 14(8):2023. https://doi.org/10.3390/ma14082023

Chicago/Turabian Style

Kawecki, Fabien; Galbraith, Todd; Clafshenkel, William P.; Fortin, Michel; Auger, François A.; Fradette, Julie. 2021. "In Vitro Prevascularization of Self-Assembled Human Bone-Like Tissues and Preclinical Assessment Using a Rat Calvarial Bone Defect Model" Materials 14, no. 8: 2023. https://doi.org/10.3390/ma14082023

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