title: Injectable in situ crosslinkable RGD-modified alginate matrix for endothelial cells delivery.
abstract: Cell-based therapies offer an attractive approach for revascularization and regeneration of tissues. However, and despite the pressing clinical needs for effective revascularization strategies, the successful immobilization of viable vascular cells within 3D matrices has been difficult to achieve. In this paper the in vitro potential of a natural, injectable RGD-alginate hydrogel as an in situ forming matrix to deliver endothelial cells was evaluated. Several techniques were employed to investigate how these microenvironments could influence the behavior of vascular cells, namely their ability to promote the outward migration of viable, proliferative cells, retaining the ability to form a 3D arrangement. Cells within RGD-grafted alginate hydrogel were able to proliferate and maintained 80% of viability for at least 48 h post-immobilization. Additionally, entrapped cells created a 3D organization into cellular networks and, when put in contact with matrigel, cells migrated out of the RGD-matrix. Overall, the obtained results support the idea that the RGD peptides conjugated to alginate provide a 3D environment for endothelial cells adhesion, survival, migration and organization.
authors.affiliation: INEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, n° 823, 4150-180 Porto, Portugal.
authors.forename: Sílvia J
authors.initials: SJ
authors.lastname: Bidarra
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Barrias
authors.forename: Keila B
authors.initials: KB
authors.lastname: Fonseca
authors.forename: Mário A
authors.initials: MA
authors.lastname: Barbosa
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Soares
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Granja
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology; D007267:Injections; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D012996:Solutions; D013388:Succinimides / Q000378:metabolism
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000464:Alginates; D042702:Angiopoietin-2; D003432:Cross-Linking Reagents; D005452:Fluoresceins; D020100:Hydrogels; D009842:Oligopeptides; D012996:Solutions; D013388:Succinimides; C047981:arginyl-glycyl-aspartic acid; D020782:Matrix Metalloproteinases