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González‐Pérez, Fernando; Alonso, Matilde; González de Torre, Israel; Santos, Mercedes; Rodríguez‐Cabello, José Carlos
Advanced healthcare materials, 11/2022, Volume: 11, Issue: 22Journal Article
Spatiotemporal control of vascularization and innervation is a desired hallmark in advanced tissue regeneration. For this purpose, we design a 3D model scaffold, based on elastin‐like recombinamer (ELR) hydrogels. This contains two interior and well‐defined areas, small cylinders, with differentiated bioactivities with respect to the bulk. Both are constructed on a protease sensitive ELR with a fast‐proteolyzed domain, but one bears a VEGF‐mimetic peptide (QK) and the other a laminin‐derived pentapeptide (IKVAV), to promote angiogenesis and neurogenesis, respectively. The outer bulk 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 of endothelial cell and axon spreading, respectively. The subcutaneous implantation of the final 3D scaffold demonstrates the ability to spatiotemporally control angiogenesis and neurogenesis in vivo. Specifically, the inner small cylinder containing the QK peptide promotes fast endothelialization, whereas the one with IKVAV peptide promotes fast neurogenesis. Both, vascularization and innervation take place in advance of the bulk scaffold infiltration. This scaffold shows that it is possible to induce vascularization and innervation in predetermined areas of the scaffold well ahead to the bulk infiltration. That significantly increases the efficiency of the regenerative activity. Herein, a 3D model scaffold containing two cylindrical elastin‐like recombinamer (ELR) hydrogels embedded in a slow‐resorbable or nonprotease‐sensitive ELR hydrogel that allow the independent spatiotemporal control of angiogenesis and neurogenesis in vivo, by the combination of protease‐sensitive sequences, with fast and slow degradation kinetics, a VEGF‐mimetic peptide (QK), and a laminin‐derived peptide (IKVAV) is developed.
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