PLLA/POSS Nanofibers Loaded with Multitargeted pANG Composite Nanoparticles for Promotion of Vascularization in Shear Flow.

In vitro prevascularization is particularly important for the clinical application of tissue engineering scaffolds that require vascularization. The principal challenge is simulating the dynamic in vivo environment to promote the continuous growth of blood vessels. In this study, two targeting polypeptides are linked to the two ends of an amphiphilic block copolymer, polyethyleneimine-b-poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)-b-polyethyleneimine (PEI-PLMD-PEI), and self-assembled to form positively charged nanoparticles (NPs), which can bind to negatively charged pANG through electrostatic interactions; the polypeptides are finally loaded into PLLA/polyhedral oligomeric silsesquioxane (POSS) porous fibers to prepare untargeted nanofibers (unTFs), targeted porous nanofibers (TFBs), and targeted nanofiber bundles. The effects of the porous nanofibers on human umbilical vein endothelial cell (HUVEC) transfection, spreading, proliferation, morphology, and expression of related factors are investigated under the action of shear flow force. The results show that the PLLA/POSS nanofibers can maintain stable release of multitargeted NPs for nearly 45 days. Both the dual-targeted porous NPs and shear flow improve the pANG transfection efficiency and promote cell proliferation, and they have a good synergistic effect. These results provide a potential strategy for designing HUVEC-specific gene carriers and using shear flow to enhance endothelialization.