Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle.

Authors

Qixu Zhang, The University of Texas MD Anderson Cancer Center,
Justin Hubenak, The University of Texas MD Anderson Cancer Center,
Tejaswi Iyyanki, The University of Texas MD Anderson Cancer Center,
Erik Alred, The University of Texas MD Anderson Cancer Center,
Kristin C Turza, The University of Texas MD Anderson Cancer Center,
Gregory Davis MD, Lehigh Valley Health NetworkFollow
Edward I Chang, The University of Texas MD Anderson Cancer Center,
Cynthia D Branch-Brooks, The University of Texas MD Anderson Cancer Center,
Elisabeth K Beahm, The University of Texas MD Anderson Cancer Center,
Charles E Butler, The University of Texas MD Anderson Cancer Center,

Publication/Presentation Date

12-1-2015

Abstract

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold-stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model-hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber-provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects.

Volume

73

First Page

198

Last Page

213

ISSN

1878-5905

Published In/Presented At

Zhang, Q., Hubenak, J., Iyyanki, T., Alred, E., Turza, K. C., Davis, G., Chang, E. I., Branch-Brooks, C. D., Beahm, E. K., & Butler, C. E. (2015). Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle. Biomaterials, 73, 198–213. https://doi.org/10.1016/j.biomaterials.2015.09.024

Disciplines

Medicine and Health Sciences

PubMedID

26410787

Department(s)

Department of Surgery

Document Type

Article