Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells

Mitchell A. Kuss, Robert Harms, Shaohua Wu, Ying Wang, Jason B. Untrauer, Mark Alan Carlson, Bin Duan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Reconstruction of complex, craniofacial bone defects often requires autogenous vascularized bone grafts, and still remains a challenge today. In order to address this issue, we isolated the stromal vascular fraction (SVF) from adipose tissues and maintained the phenotypes and the growth of endothelial lineage cells within SVF derived cells (SVFC) by incorporating an endothelial cell medium. We 3D bioprinted SVFC within our hydrogel bioinks and conditioned the constructs in either normoxia or hypoxia. We found that short-term hypoxic conditioning promoted vascularization-related gene expression, whereas long-term hypoxia impaired cell viability and vascularization. 3D bioprinted bone constructs composed of polycaprolactone/hydroxyapatite (PCL/HAp) and SVFC-laden hydrogel bioinks were then implanted into athymic mice, after conditioning in normoxic or short-term hypoxic environments, in order to determine the in vitro and in vivo vascularization and osteogenic differentiation of the constructs. Short-term hypoxic conditioning promoted microvessel formation in vitro and in vivo and promoted integration with existing host vasculature, but did not affect osteogenic differentiation of SVFC. These findings demonstrate the benefit of short-term hypoxia and the potential for utilization of SVFC and 3D bioprinting for generating prevascularized 3D bioprinted bone constructs. Furthermore, the ability to custom design complex anatomical shapes has promising applications for the regeneration of both large and small craniofacial bone defects.

Original languageEnglish (US)
Pages (from-to)29312-29320
Number of pages9
JournalRSC Advances
Volume7
Issue number47
DOIs
StatePublished - Jan 1 2017

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Bone
Hydrogel
Endothelial cells
Hydrogels
Polycaprolactone
Defects
Durapatite
Hydroxyapatite
Gene expression
Grafts
Cells
Tissue

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells. / Kuss, Mitchell A.; Harms, Robert; Wu, Shaohua; Wang, Ying; Untrauer, Jason B.; Carlson, Mark Alan; Duan, Bin.

In: RSC Advances, Vol. 7, No. 47, 01.01.2017, p. 29312-29320.

Research output: Contribution to journalArticle

Kuss, Mitchell A. ; Harms, Robert ; Wu, Shaohua ; Wang, Ying ; Untrauer, Jason B. ; Carlson, Mark Alan ; Duan, Bin. / Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells. In: RSC Advances. 2017 ; Vol. 7, No. 47. pp. 29312-29320.
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