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Biomaterials. 2016 Jan;77:255-66. doi: 10.1016/j.biomaterials.2015.10.026. Epub 2015 Oct 22.

Effect of prevascularization on in vivo vascularization of poly(propylene fumarate)/fibrin scaffolds.

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Department of Plastic Surgery, The Ohio State University, Columbus, OH, USA.
Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA; Research Service, Edward Hines Jr. V.A. Hospital, Hines, IL, USA.
Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
Department of Plastic Surgery, The Ohio State University, Columbus, OH, USA. Electronic address:


The importance of vascularization in the field of bone tissue engineering has been established by previous studies. The present work proposes a novel poly(propylene fumarate) (PPF)/fibrin composite scaffold for the development of vascularized neobone tissue. The effect of prevascularization (i.e., in vitro pre-culture prior to implantation) with human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on in vivo vascularization of scaffolds was determined. Five conditions were studied: no pre-culture (NP), 1 week pre-culture (1P), 2 week pre-culture (2P), 3 week pre-culture (3P), and scaffolds without cells (control, C). Scaffolds were implanted subcutaneously in a severe combined immunodeficiency (SCID) mouse model for 9 days. During in vitro studies, CD31 staining showed a significant increase in vascular network area over 3 weeks of culture. Vascular density was significantly higher in vivo when comparing the NP and 3P groups. Immunohistochemical staining of human CD-31 expression indicated spreading of vascular networks with increasing pre-culture time. These vascular networks were perfused with mouse blood indicated by perfused lectin staining in human CD-31 positive vessels. Our results demonstrate that in vitro prevascularization supports in vivo vascularization in PPF/fibrin scaffolds.


Fibrinogen; Human umbilical vein endothelial cells (HUVECs); Mesenchymal stem cells (MSCs); Poly(propylene fumarate) (PPF); Thrombin

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