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Int J Low Extrem Wounds. 2015 Jun;14(2):146-53. doi: 10.1177/1534734615580018. Epub 2015 Jun 1.

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing.

Author information

1
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
2
Department of Biomedical Engineering, University of California, Davis, CA, USA.
3
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
4
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
5
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA Harvard School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
6
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA aveves@bidmc.harvard.edu.

Abstract

Diabetic foot ulcers (DFU) represent a severe health problem and an unmet clinical challenge. In this study, we tested the efficacy of novel biomaterials in improving wound healing in mouse models of diabetes mellitus (DM). The biomaterials are composed of alginate- and deoxyribonucleic acid (DNA)-based gels that allow incorporation of effector cells, such as outgrowth endothelial cells (OEC), and provide sustained release of bioactive factors, such as neuropeptides and growth factors, which have been previously validated in experimental models of DM wound healing or hind limb ischemia. We tested these biomaterials in mice and demonstrate that they are biocompatible and can be injected into the wound margins without major adverse effects. In addition, we show that the combination of OEC and the neuropeptide Substance P has a better healing outcome than the delivery of OEC alone, while subtherapeutic doses of vascular endothelial growth factor (VEGF) are required for the transplanted cells to exert their beneficial effects in wound healing. In summary, alginate and DNA scaffolds could serve as potential delivery systems for the next-generation DFU therapies.

KEYWORDS:

biomaterials; diabetic foot ulcers; endothelial precursor cells; neuropeptides; wound healing

PMID:
26032947
DOI:
10.1177/1534734615580018
[Indexed for MEDLINE]
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