PLGA-liposome electrospun fiber delivery of miR-145 and PDGF-BB synergistically promoted wound healing

Abstract

It has been shown that mesenchymal stromal cells (MSC)-based tissue engineering has potential clinical application because of its paracrine effect, differentiation ability and high availability. However, its application is limited due to low differentiation efficiency. It has been reported that microRNA 145 (miR-145) and platelet-derived growth factor (PDGF) play a critical role in the differentiation of MSC into vascular smooth muscle cells (VSMC). In the present study, we evaluated whether miR-145 and PDGF-BB would synergistically stimulate the differentiation of MSC into VSMC, and whether the delivery of these components with nanoparticles would promote wound healing. Our results show that miR-145 and PDGF-BB additively stimulated the differentiation of MSC into VSMC, and that miR-145 promoted MSC differentiation through a kruppel-like factor 4 (KLF4)-dependent manner since its stimulatory effect was blocked by KLF4 overexpression. Then, we constructed poly(lactic-coglycolicacid)-liposome (PLGA-LIP) membrane. It was found that MSC grew well on this scaffold, and that PLGA-LIP engaged with miR-145 or PDGF-BB promoted tube formation in human umbilical vein endothelial cells. Further in vivo study shows that PLGA-LIP engaged with miR-145 or PDGF-BB significantly promoted wound healing and angiogenesis as indicated by the decreased wound, increased expression of CD31 and α smooth muscle actin, endothelial marker and VSMC marker respectively. Of note, the combination of miR-145 and PDGF-BB showed significantly additive protective effects on angiogenesis and wound healing when delivered with PLGA-LIP. In summary, the present study demonstrated that PLGA-LIP membranes engaged with miR-145 and PDGF-BB synergistically promoted wound healing.