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Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis.

ABSTRACT: Diabetic chronic wound, characterized by prolonged inflammation and impaired angiogenesis, has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide. Although a great variety of wound dressings have been developed, few of encouraged achievements were obtained so far. In this study, the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor (VEGF) and achieve better healing outcomes by regulating inflammation and promoting angiogenesis. The gene-activated bilayer dermal equivalents (Ga-BDEs), which has good biocompatibility, were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent. The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro. To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human, a reformative rat model of full-thickness diabetic chronic wound was adopted. Under the treatment of Ga-BDEs, speeding wound healing was observed, which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases, respectively. These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously. Subsequently, the better regeneration outcomes, including deposition of oriented collagen and fast reepithelialization, were achieved. All these results indicated that, being different from traditional pro-angiogenic concept, the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.

SUBMITTER: Lou D

PROVIDER: S-EPMC7217806 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis.

Lou Dong D Luo Yu Y Pang Qian Q Tan Wei-Qiang WQ Ma Lie L

Bioactive materials 20200508 3

Diabetic chronic wound, characterized by prolonged inflammation and impaired angiogenesis, has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide. Although a great variety of wound dressings have been developed, few of encouraged achievements were obtained so far. In this study, the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor (VEGF) and achieve better healing outcomes by regulating i ...[more]

PMID: 32420517

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Project description:Poor wound healing affects millions of people worldwide each year and needs better therapeutic strategies. Synechococcus elongatus PCC 7942 is a naturally occurring photoautotrophic cyanobacterium that can be easily obtained and large-scale expanded. Here, we investigated the therapeutic efficacy of this cyanobacterium in a mouse model of acute burn injury and whether the secretion of extracellular vesicles (EVs), important mediators of cell paracrine activity, is a key mechanism of the cyanobacterium-induced regulation of wound healing. Methods: The effects of Synechococcus elongatus PCC 7942 on burn wound healing in mice under light or dark conditions were evaluated by measuring wound closure rates, histological and immunofluorescence analyses. A series of assays in vivo and in vitro were conducted to assess the impact of the cyanobacterium on angiogenesis. GW4869 was used to interfere with the secretion of EVs by the cyanobacterium and the abilities of the GW4869-pretreated and untreated Synechococcus elongatus PCC 7942 to regulate endothelial angiogenesis were compared. The direct effects of the cyanobacterium-derived EVs (S. elongatus-EVs) on angiogenesis, wound healing and expressions of a class of pro-inflammatory factors that have regulatory roles in wound healing were also examined. Results: Synechococcus elongatus PCC 7942 treatment under light and dark conditions both significantly promoted angiogenesis and burn wound repair in mice. In vitro, the cyanobacterium enhanced angiogenic activities of endothelial cells, but the effects were markedly blocked by GW4869 pretreatment. S. elongatus-EVs were capable of augmenting endothelial angiogenesis in vitro, and stimulating new blood vessel formation and burn wound healing in mice. The expression of interleukin 6 (IL-6), which has an essential role in angiogenesis during skin wound repair, was induced in wound tissues and wound healing-related cells by S. elongatus-EVs and Synechococcus elongatus PCC 7942. Conclusion: Synechococcus elongatus PCC 7942 has the potential as a promising strategy for therapeutic angiogenesis and wound healing primarily by the delivery of functional EVs, not by its photosynthetic activity. The promotion of IL-6 expression may be a mechanism of the cyanobacterium and its EVs-induced pro-angiogenic and -wound healing effects.

Dataset Information

Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis.

Publications

Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis.

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