Fibrin‐embedded administration of VEGF plasmid enhances skin flap survival

Abstract

The aim of the present study was to experimentally evaluate whether topical fibrin-mediated administration of a vascular endothelial growth factor (VEGF)-A plasmid to the wound bed can protect skin flaps from necrosis. A plasmid expression vector containing the VEGF-A cDNA was constructed. The plasmid was then administered to the wound bed of rat abdominal skin flaps in a fibrin sealant. The percentage of viable, ischemic and necrotic tissue was assessed postoperatively as a baseline and after 3 and 7 days using digital surface area morphometry. Laser Doppler imaging of the flaps and VEGF-A Western blot analysis of flap tissue were performed to assess angiogenesis and VEGF-A tissue levels. Flaps treated with VEGF plasmids in the presence of uptake enhancing Lipofectamine transfection reagent increased flap survival 7 days postoperatively significantly associated with markedly elevated tissue perfusion and enhanced tissue VEGF-A protein expression. Our results indicate that topical fibrin-mediated administration of a VEGF-A plasmid may serve as an alternative to previous strategies in treating ischemic skin flaps. The suggested therapeutic approach is easily applicable and inexpensive in preparation. Thus, this protocol may also enhance wound healing in posttrauma skin lacerations or in skin grafts.

Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation

“…Fibrin has been used extensively as a scaffold for tissue regeneration 21,22 and controlled delivery of growth factors to accelerate wound healing [23][24][25][26] and promote vascularization. [27][28][29][30] In addition, previous studies developed methods to conjugate growth factors into fibrin hydrogels through the action of FXIII and the fibrin-binding peptide, NQEQVSP.…”

Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model

“…A previous in vivo study assessed wound healing in an epigastric flap rat model. Animals treated with VEGF plasmids and GAMs consisting of fibrin and lipofectamine showed increased vascularisation and flap survival compared to the control groups [22]. Up to now there is no study focusing on the effects of transfection-reagent enhanced in vivo co-delivery of BMP2 and BMP7 plasmids in GAMs in a segmental bone defect model.…”

“…The defect was filled with fibrin clots (V=160 µl), which served as gene activated matrix (GAM) for all groups. Beneficial effects using fibrin as GAM for gene delivery was extensively studied and previously published [21,22].…”

Liposomes in tissue engineering and regenerative medicine

“…The flap survival was enhanced by 14%, and the histological analysis showed new vessel formation [182]. A plasmid expression vector containing VEGF was constructed to be administered to the wound bed of rat abdominal skin flaps in a fibrin sealant [145]. The topical fibrin-mediated administration of a VEGF-A plasmid increased flap survival by 7 days.…”