期刊
ADVANCED HEALTHCARE MATERIALS
卷 11, 期 22, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202201646
关键词
elastin-like recombinamers; hydrogels; innervation; tunable proteolytic sequences; vascularization
资金
- Spanish Government [RTI2018-096320-B-C22, FPU16-04015, PID2019-110709RB-I00, PID2020-118669RA-I00]
- Interreg V Espana Portugal POCTEP [0624_2IQBIONEURO_6_E]
- Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y Leon
This study presents a 3D scaffold based on elastin-like recombinamer hydrogels for spatiotemporal control of vascularization and innervation in tissue regeneration. In vitro studies show the promotion of endothelial cell and axon spreading by the designed scaffold. Subcutaneous implantation experiments demonstrate the ability of the scaffold to induce angiogenesis and neurogenesis in predetermined areas.
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.
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