Chemically Modified SDF-1α mRNA Promotes Random Flap Survival by Activating the SDF-1α/CXCR4 Axis in Rats

2019 ◽  
Author(s):  
Zucheng Luo ◽  
Yujie Bian ◽  
Gang Zheng ◽  
Hui Jing Wang ◽  
Bingqian Yan ◽  
...  
Keyword(s):  
Flap Survival ◽  
Chemically Modified ◽  
Cxcr4 Axis

scholarly journals Chemically Modified SDF-1α mRNA Promotes Random Flap Survival by Activating the SDF-1α/CXCR4 Axis in Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Zucheng Luo ◽  
Yujie Bian ◽  
Gang Zheng ◽  
Huijing Wang ◽  
Bingqian Yan ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Skin Flap ◽  
Tumor Resection ◽  
Skin Flaps ◽  
Chemically Modified ◽  
Congenital Deformities ◽  
Stat3 Signaling ◽  
Stromal Cell Derived Factor ◽  
And Migration ◽  
Cxcr4 Axis

Random skin flaps are frequently applied in plastic and reconstructive surgery for patients suffering from soft tissue defects caused by congenital deformities, trauma and tumor resection. However, ischemia and necrosis in distal parts of random skin flaps remains a common challenge that limits the clinical application of this procedure. Recently, chemically modified mRNA (modRNA) was found to have great therapeutic potential. Here, we explored the potential of fibroblasts engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) to improve vascularization and survival of therapeutic random skin flaps. Our study showed that fibroblasts pre-treated with SDF-1α modRNA have the potential to salvage ischemic skin flaps. Through a detailed analysis, we revealed that a fibroblast SDF-1α modRNA combinatorial treatment dramatically reduced tissue necrosis and significantly promoted neovascularization in random skin flaps compared to that in the control and vehicle groups. Moreover, SDF-1α modRNA transcription in fibroblasts promoted activation of the SDF-1α/CXCR4 pathway, with concomitant inactivation of the MEK/ERK, PI3K/AKT, and JAK2/STAT3 signaling pathways, indicating a possible correlation with cell proliferation and migration. Therefore, fibroblast-mediated SDF-1α modRNA expression represents a promising strategy for random skin flap regeneration.

Binding of Tissue Plasminogen Activator to Vascular Grafts

1989 ◽  
Vol 61 (01) ◽  
pp. 131-136 ◽  
Author(s):  
Richard A Harvey ◽  
Hugh C Kim ◽  
Jonathan Pincus ◽  
Stanley Z Trooskin ◽  
Josiah N Wilcox ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Polymer Surface ◽  
Enzymic Activity ◽  
Vascular Prostheses ◽  
Chemically Modified ◽  
Insoluble Surfactant ◽  
Tissue Plasminogen

SummaryTissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDM AC). Surfactant- treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I- tPA (5-30 μg 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t½ of appoximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.

ROLE OF rhBMP-2 AND rhBMP-7 IN THE METABOLISM AND DIFFERENTIATION OF OSTEOBLAST-LIKE CELLS CULTURED ON CHEMICALLY MODIFIED TITANIUM SURFACES

2012 ◽  
pp. 141208072802005
Author(s):  
Fabiano Ribeiro Cirano ◽  
ADRIANE TOGASHI ◽  
MARCIA MARQUES ◽  
FRANCISCO PUSTIGLIONI ◽  
LUIZ LIMA
Keyword(s):  
Chemically Modified ◽  
Titanium Surfaces ◽  
Cells Cultured
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