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Enhanced wound vascularization using a dsASCs seeded FPEG scaffold

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Abstract

The bioengineering of autologous vascular networks is of great importance in wound healing. Adipose-derived stem cells (ASCs) are of interest due to their ability to differentiate toward various cell types, including vascular. We hypothesized that adult human ASCs embedded in a three-dimensional PEG-fibrin (FPEG) gel have the ability to modulate vascularization of a healing wound. Initial in vitro characterization of ASCs isolated from discarded burn skin samples (dsASCs) and embedded in FPEG gels indicated they could express such pericyte/smooth muscle cell markers as α-smooth muscle actin, platelet-derived growth factor receptor-β, NG2 proteoglycan, and angiopoietin-1, suggesting that these cells could potentially be involved in a supportive cell role (i.e., pericyte/mural cell) for blood vessels. Using a rat skin excision model, wounds treated with dsASCs-FPEG gels showed earlier collagen deposition and wound remodeling compared to vehicle FPEG treated wounds. Furthermore, the dsASCs-seeded gels increased the number of vessels in the wound per square millimeter by day 16 (~66.7 vs. ~36.9/mm2) in these same studies. dsASCs may support this increase in vascularization through their trophic contribution of vascular endothelial growth factor, as determined by in vitro analysis of mRNA and the protein levels. Immunohistochemistry showed that dsASCs were localized to the surrounding regions of large blood-perfused vessels. Human dsASCs may play a supportive role in the formation of vascular structures in the healing wound through direct mechanisms as well as indirect trophic effects. The merging of autologous grafts or bioengineered composites with the host’s vasculature is critical, and the use of autologous dsASCs in these procedures may prove to be therapeutic.

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Acknowledgments

Dr. Natesan is supported by a Postdoctoral Fellowship Grant from the Pittsburgh Tissue Engineering Initiative (PTEI). Funding for this work was provided by the TATRC Foundation and the Deployment Related Medical Research Program.

Conflict of interest

The opinions or assertions contained herein are the private views of RJC and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

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Authors and Affiliations

  1. Regenerative Medicine Research Program, United States Army Institute of Surgical Research, 3698 Chambers Pass, BHT 1: Bldg 3611, Fort Sam Houston, TX, 78234-6315, USA

    David O. Zamora, Shanmugasundaram Natesan, Sandra Becerra, Nicole Wrice & Robert J. Christy

  2. Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, Austin, TX, 78712-0238, USA

    Eunna Chung & Laura J. Suggs

Authors
  1. David O. Zamora
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  2. Shanmugasundaram Natesan
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  3. Sandra Becerra
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  4. Nicole Wrice
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  5. Eunna Chung
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  6. Laura J. Suggs
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  7. Robert J. Christy
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Correspondence to Robert J. Christy.

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Disclaimer: The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of Defense or Department of Army. The authors are employees of the U.S. Government, and this work was prepared as part of their official duties. This research was funded by the U.S. Army Medical Research and Materiel Command. This study has been conducted in compliance with the Animal Welfare Act, the implementing Animal Welfare Regulations, and the principles of the Guide for the Care and Use of Laboratory Animals.

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Zamora, D.O., Natesan, S., Becerra, S. et al. Enhanced wound vascularization using a dsASCs seeded FPEG scaffold. Angiogenesis 16, 745–757 (2013). https://doi.org/10.1007/s10456-013-9352-y

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  • DOI: https://doi.org/10.1007/s10456-013-9352-y

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