Protease‐sensitive, VEGF‐mimetic peptide, and IKVAV laminin‐derived peptide sequences within elastin‐like recombinamer scaffolds provide spatiotemporally synchronized guidance of angiogenesis and neurogenesis

Abstract

Spatiotemporal control of vascularization and innervation is a desiredhallmark in advanced tissue regeneration. For this purpose, we design a 3Dmodel scaffold, based on elastin-like recombinamer (ELR) hydrogels. Thiscontains two interior and well-defined areas, small cylinders, withdifferentiated bioactivities with respect to the bulk. Both are constructed on aprotease sensitive ELR with a fast-proteolyzed domain, but one bears aVEGF-mimetic peptide (QK) and the other a laminin-derived pentapeptide(IKVAV), to promote angiogenesis and neurogenesis, respectively. The outerbulk is based on a slow proteolytic sequence and RGD cell adhesion domains.In vitro studies show the effect of QK and IKVAV peptides on the promotion ofendothelial cell and axon spreading, respectively. The subcutaneousimplantation of the final 3D scaffold demonstrates the ability tospatiotemporally control angiogenesis and neurogenesis in vivo. Specifically,the inner small cylinder containing the QK peptide promotes fastendothelialization, whereas the one with IKVAV peptide promotes fastneurogenesis. Both, vascularization and innervation take place in advance ofthe bulk scaffold infiltration. This scaffold shows that it is possible to inducevascularization and innervation in predetermined areas of the scaffold wellahead to the bulk infiltration. That significantly increases the efficiency of theregenerative activity.