title: Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing.
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.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Tellechea
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA, USA.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Silva
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Min
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ermelindo C
authors.initials: EC
authors.lastname: Leal
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Auster
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Pradhan-Nabzdyk
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Shih
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA Harvard School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA aveves@bidmc.harvard.edu.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Veves
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001458:Bandages; D001672:Biocompatible Materials / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D017719:Diabetic Foot / Q000188:drug therapy*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005782:Gels; D020723:Glucuronic Acid / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D042461:Vascular Endothelial Growth Factor A; D020723:Glucuronic Acid
keywords: biomaterials; diabetic foot ulcers; endothelial precursor cells; neuropeptides; wound healing